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Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2006. / Härtill 4 uppsatser.

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2013-04-04T12:51:40Z No. of bitstreams: 1 Tese - Caline Gomes Ferraz.pdf: 17842899 bytes, checksum: 461e8d2ed5b07ba0d75417b8abbfe63b (MD5) / Approved for entry into archive by Ana Hilda Fonseca(anahilda@ufba.br) on 2013-04-29T14:58:51Z (GMT) No. of bitstreams: 1 Tese - Caline Gomes Ferraz.pdf: 17842899 bytes, checksum: 461e8d2ed5b07ba0d75417b8abbfe63b (MD5) / Made available in DSpace on 2013-04-29T14:58:51Z (GMT). No. of bitstreams: 1 Tese - Caline Gomes Ferraz.pdf: 17842899 bytes, checksum: 461e8d2ed5b07ba0d75417b8abbfe63b (MD5) Previous issue date: 2011 / CAPES / O presente trabalho relata o estudo fitoquímico do caule da espécie Clusia burlemarxii (Clusiaceae), coletada nas proximidades da Cachoeira do Fraga no município de Rio de Contas e Mucugê na Chapada Diamantina-BA, Do estudo deste extrato permitiu o isolamento, identificação e determinação de seis metabólitos inéditos denominados: isopropolona A, burlemarxionas A, B, C, D e E e dezesseis substâncias conhecidas: as benzofenonas polipreniladas, propolona A, sampsoniona B, sampsoniona N, obdeltifoliona C; os triterpenos, friedelina, friedelinol, ácido betulínico, betulinaldeído, lupeol, eufol e butirospermol; os esteróides, sitosterol, estigmasterol e sitostenona; uma bifenila a 2,2-dimetil-5-hidroxi-7-fenilcromeno e uma xantona a brasilixantona B. A determinação estrutural dos metabólitos secundários isolados foi realizada através de técnicas espectrométricas como: Infravermelho, EM e Ressonância Magnética Nuclear de Hidrogênio-1 e Carbono-13, DEPT, HMBC, HMQC juntamente com comparação dos dados descritos na literatura. As substâncias propolona A, sampsoniona N e burlemarxiona A, tiveram sua citotoxicidade contra Células de Glioblastoma Humano GL-15 avaliada. / Salvador

Orientador: Anita Jocelyne Marsaioli / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-12T23:58:46Z (GMT). No. of bitstreams: 1 Machado_SamisiaMariaFernandes_D.pdf: 2203319 bytes, checksum: 2757bcd8b8a518e49e0692412267fbb3 (MD5) Previous issue date: 2002 / Resumo: Este trabalho tem como objetivo principal dar continuidade aos estudos fitoquímicos das resinas florais de espécies do gênero Clusia e expandir estes estudos ao gênero Tovomitopsis, ambos pertencentes à família Gittiferae. Os resultados e discussões foram divididos em quatro capítulos. O primeiro capítulo refere-se ao estudo das resinas florais das espécies C. hilariana branca masculina e C. insignis masculina, cultivadas em Campinas/SP, C. scrobiculata hermafrodita procedente da Amazônia e T. saldanhae, espécie rara procedente do sudoeste do Brasil. Este estudo resultou no isolamento de 7 benzofenonas poliisopreniladas das quais 4 são inéditas. O isolamento desta classe de metabólitos secundários na resina floral de T. saldanhae indicou que as resinas florais como recompensa em ambos os gêneros surgiram antes da separação destes, sendo esta uma contribuição valiosa na escala evolutiva desta família. O segundo capítulo relata a composição química dos exsudatos estigmáticos das flores masculinas com pistilóides das espécies C. renggerioides, C. paralicola, C. weddelliana e das flores femininas das espécies C. spiritu-sanctensis e C. panapanari, todas pertencentes à seção Cordylandra. As análises de CG/EM dos exsudatos estigmáticos metilados mostraram que estes são compostos por ácidos graxos de cadeia longa. Esta composição permitiu sugerir o mecanismo químico pelo qual estes ácidos participam do processo de polinização das clúsias. O terceiro capítulo refere-se à proposta de uma rota sintética, com base em propostas biogenéticas, para as benzofenonas poliisopreniladas isoladas. Finalmente, o último capítulo deste trabalho relata algumas discussões relacionadas à configuração absoluta das benzofenonas poliisopreniladas isoladas / Abstract: This thesis has the objective of concluding the chemical investigations on the floral resins of Clusia and its components and expanding it to Tovomitopsis, both genus belong to the Guttiferae family. The results and discussions were divided into four different chapters. The first part is related to the chemical composition of C. hilariana white male and C. insignis male both species cultivated in Campinas, C. scrobiculata hermafrodita from Amazon and Tovomitopsis saldanhae from southwestern part of Brasil. From these we have isolated 7 poliisoprenylated benzophenones, 4 of which were novel. The isolation of this class of secondary metabolites from the floral resin of T. saldanhae was indicative that the floral resins were present in a common ancestor, thus a this study was a contribution to the evolution of this family. The second part of this work reports the chemical composition of the stigmatic exudates of the male flowers with pistilodium of C. renggeroides, C. paralicola, C. weddeliana and female flowers of C. spiritu-sanctensis and C. panapanari, all of these belonging to the section Condylandra. The GC/MS analysis of the methylated stigmatic exudates revealed that they are composed of long chain carbonxylic acids. The mechanism of pollination was proposed based on this chemical composition. The synthesis of the benzolupulone is discussed in chapter 3 and finally in the fourth chapter there are some discussions related to the absolute configuration of the isolated poliisoprenylated benzophenones / Doutorado / Quimica Organica / Doutor em Ciências

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-09-15T15:28:18Z No. of bitstreams: 1 Dissertação Caline Gomes Ferraz.pdf: 5892044 bytes, checksum: c69c009c9c27a1226b6cad92dfad11f6 (MD5) / Approved for entry into archive by Vanessa Reis (vanessa.jamile@ufba.br) on 2016-09-15T15:42:14Z (GMT) No. of bitstreams: 1 Dissertação Caline Gomes Ferraz.pdf: 5892044 bytes, checksum: c69c009c9c27a1226b6cad92dfad11f6 (MD5) / Made available in DSpace on 2016-09-15T15:42:14Z (GMT). No. of bitstreams: 1 Dissertação Caline Gomes Ferraz.pdf: 5892044 bytes, checksum: c69c009c9c27a1226b6cad92dfad11f6 (MD5) / Capes / O presente trabalho relata o estudo fotoquímico do extrato hexânico do caule de Clusia burle-marxii (Clusiaceae). O espécime foi coletado nas proximidades da Cachoeira do Fraga no município de Rio de Contas, Chapada Diamantina, Bahia. Do extrato hexânico do caule possibilitou o isolamento, identificação e determinação de algumas classes de metabólitos. Foram isolados dois triterpenos, quatro esteróides, dez benzofenonas e dez ésteres graxos. Estas substâncias foram obtidas por processos de fracionamento em coluna cromatográfica e cromatografia em camada delgada preparativa. Os triterpenos (Friedelina e Friedelinol), os esteróides (β- Sitosterol, Estigmast-5-eno-3β,7β-diol, Estigmast-5-eno-3β,7α-diol, Estigmast-7-en- 3β-ol-6-ona) e a benzofenona (Nemorosonol) foram identificadas por analises de RMN de 1H e RMN de 13 C, DEPT e por comparação com os dados descritos na literatura. Este procedimento foi usado para determinação estrutural do esteróide inédito Estigmast-7- en- 3β-ol-6-ona. Os ésteres graxos (Tetradeconoato de metila, Pentadeconoato de metila, Hexadecanoato de metila, Heptadecanoato de metila, Octadenoato de metila, Nonadeconoato de metila, Eicosanoato de metila e Docosonoato de metila) foram identificados após analise de EM. Para determinação estrutural da benzofenona inédita foram utlilizadas as técnicas de RMN de 1H e RMN de 13C, DEPT, HMBC, HSQC. / The present work described the phytochemistry study the wood hexane extracts studies of specie Clusia burle-marxii. The specie was collected nearby Cachoeira do Fraga in the Rio de Contas, Chapada Diamantina, Bahia, Brazil. The wood hexane extracts allowed the isolations, identification and structural determination of some metabolites class. Two triterpenes, four steroids, ten benzophenones, ten fatty esters. These substances were obtained by fractionation through preparative thin layer chromatographyc and chromatographyc column. The triterpenes ( Friedeline and Friedelinol), the steroids (β- Sitosterol, Stigmast-5-ene- 3β,7β-diol, Stigmast-5-ene-3β,7α-diol, and the benzophenone (Nemorosonol) were identified by 1H NMR and 13C NMR, DEPT analysis and comparson with the data from literature. This same procedure was used in the novel steroid Stigmast-7-en- 3β-ol-6- ona structural determination. The fatty esters (methyl tetradecanoate, methyl pentadecanoate, methyl hexadecanoate, methyl heptadecanoate, methyl octadecanoate, methyl nonadecanoate, methyl eicisanoate and methyl docosanoate) were identified by MS analysis. The structural determination of the new benzophenone was performed by NMR spectrocopyc techniques (1H NMR and 13C NMR, DEPT, HMBC, HMQC).

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2013-04-09T14:23:55Z No. of bitstreams: 1 Dissertação corrigifa aos defesa.pdf: 1579566 bytes, checksum: 212d44a2c53e2dbbae9af296ae48959c (MD5) / Approved for entry into archive by Ana Hilda Fonseca(anahilda@ufba.br) on 2013-04-19T12:56:31Z (GMT) No. of bitstreams: 1 Dissertação corrigifa aos defesa.pdf: 1579566 bytes, checksum: 212d44a2c53e2dbbae9af296ae48959c (MD5) / Made available in DSpace on 2013-04-19T12:56:31Z (GMT). No. of bitstreams: 1 Dissertação corrigifa aos defesa.pdf: 1579566 bytes, checksum: 212d44a2c53e2dbbae9af296ae48959c (MD5) Previous issue date: 2010 / CAPES / Própolis é uma mistura complexa, formada basicamente por secreções salivares das abelhas e por um material resinoso e balsâmico coletado por elas dos ramos, flores, pólen, brotos e exsudados de árvores, à qual têm sido atribuídas propriedades antimicrobiana, antioxidante, antiinflamatória, antiviral entre outras. Sua composição varia com a flora da região e época da colheita. Este trabalho descreve o perfil cromatográfico dos extratos hexânicos e metanólicos da própolis da Bahia obtidos por maceração, bem como o isolamento e a elucidação estrutural de algumas substâncias presentes na fase hexânica da própolis marrom clara, e avaliação da atividade antioxidante e citotóxica dos extratos. Utilizando-se métodos cromatográficos usuais (CC, CCDC e CCDP) foram isolados do extrato hexânico o trans cinamato de metila, o cinamato de sitosterila que tem seu primeiro relato na própolis, além de duas benzofenonas a hyperibona A e a clusianona, esta última também identificada pela primeira vez na própolis. As estruturas das substâncias isoladas foram elucidadas através da análise dos dados obtidos pelos espectros no IV, de RMN de 1H, 13 C, DEPT, além de técnicas bidimensionais (COSY, HMBC e HMQC). Os testes de atividade antioxidante in vitro utilizando a metodologia do seqüestro do radical estável DPPH, demostraram que os extratos apresentaram moderada atividade antioxidante quando comparados com o padrão ácido gálico. Nos ensaios de atividade citotóxica frente Artemia salina os extratos apresentaram CL50 < 145 ug/mL podendo ser um indicativo de atividade antitumoral. / Salvador

<p>Benzofenoni&nbsp; i&nbsp; kofein&nbsp; su&nbsp; sveprisutni,&nbsp; kako&nbsp; u&nbsp; otpadnim,&nbsp; tako&nbsp; i&nbsp; u<br />povr&scaron;inskim vodama, u koncentracijama od nekoliko ng/l do mg/l. Koriste se<br />u proizvodnji kozmetičkih preparata, kao&nbsp; pojačivači mirisa i ukusa, fiksatori<br />u&nbsp; parfemima,&nbsp; aditivi&nbsp; u&nbsp; plastici,&nbsp; sredstvima&nbsp; za&nbsp; či&scaron;ćenje,&nbsp; u&nbsp; proizvodnji<br />pesticida.&nbsp; Benzofenoni&nbsp; su&nbsp; UV&nbsp; filteri&nbsp; pa&nbsp; se&nbsp; često&nbsp; koriste&nbsp; u&nbsp; proizvodnji<br />sunčanih&nbsp; naočara,&nbsp; kao&nbsp; i&nbsp; u&nbsp; proizvodnji&nbsp; sapuna&nbsp; i&nbsp; parfema,&nbsp; sprečavajući&nbsp; UV<br />zrake&nbsp; da&nbsp; o&scaron;tete&nbsp; miris&nbsp; ili&nbsp; boju&nbsp; proizvoda.&nbsp; BP-3&nbsp; se&nbsp; najče&scaron;će&nbsp; koristi&nbsp; u<br />kozmetičkoj&nbsp; industriji&nbsp; kao&nbsp; UV&nbsp; filter&nbsp; u&nbsp; kremama&nbsp; za&nbsp; sunčanje,&nbsp; losionima&nbsp; za<br />telo,&nbsp; &scaron;amponima,&nbsp; bojama&nbsp; i&nbsp; sprejevima&nbsp; za&nbsp; kosu.&nbsp; Kofein&nbsp; se&nbsp; primenjuje&nbsp; u<br />proizvodnji&nbsp; prehrambenih&nbsp; proizvoda,&nbsp; lekova&nbsp; i&nbsp; kozmetičkih&nbsp; preparata.<br />Značajno&nbsp; se&nbsp; razlikuju&nbsp; po&nbsp; hidrofilnosti&nbsp; (benzofenon&nbsp; log&nbsp; Kow&nbsp; 3,18;<br />benzofenon-3&nbsp; log&nbsp; Kow&nbsp; 3,79;&nbsp; kofein&nbsp; log&nbsp; Kow&nbsp; -0,07).&nbsp; Usled&nbsp; nedostatka<br />podataka o sadržaju odabranih predstavnika benzofenona (benzofenon (BP) i<br />benzofenon-3(BP-3)) i kofeina (CF)&nbsp; u različitim tipovima vode&nbsp; (pre svega u<br />lokalnim&nbsp; otpadnim&nbsp; vodama&nbsp; i&nbsp; rečnoj&nbsp; vodi)&nbsp; i&nbsp; njihovom&nbsp; pona&scaron;anju&nbsp; u<br />tretmanima&nbsp; voda,&nbsp; izvr&scaron;ena&nbsp; su&nbsp; ispitivanja&nbsp; u&nbsp; efluentu&nbsp; tipičnog&nbsp; postrojenja&nbsp; za<br />preradu&nbsp; otpadnih&nbsp; voda&nbsp; i&nbsp; rečnoj&nbsp; vodi&nbsp; Dunava.&nbsp; Utvrđeno&nbsp; je&nbsp; da&nbsp; su&nbsp; sve&nbsp; tri<br />komponente&nbsp; prisutne&nbsp; u&nbsp; efluentu&nbsp; WWTP&nbsp; (BP&nbsp; od&nbsp; 0,112&nbsp; &micro;g/l&nbsp; do&nbsp; 0,146&nbsp; &micro;g/l;<br />BP-3 od 0,00718 &micro;g/l do 0,42 &micro;g/l; CF od 0,2 &micro;g/l do 12 &micro;g/l) i u Dunavu<br />(maksimalno detektovana koncentracija je za BP 0,95 &micro;g/l, za BP-3 0,62 &micro;g/l<br />i&nbsp; za&nbsp; CF&nbsp; 0,7&nbsp; &micro;g/l).&nbsp; Pored&nbsp; ispitivanja&nbsp; sadržaja&nbsp; ovih&nbsp; jedinjenja&nbsp; ispitana&nbsp; je<br />efikasnost nekonvencionalnih procesa u obradi efluenta WWTP&nbsp; (adsorpcija,<br />koagulacije,&nbsp; PAC/CoA,&nbsp; PAC/UF)&nbsp; i&nbsp; konvencionalnih&nbsp; (adsorpcija,<br />koagulacija)&nbsp; i&nbsp; nekonvencionalnih procesa (PAC/CoA, PAC/UF, CoA/UF)&nbsp; u<br />obradi&nbsp; rečne&nbsp; vode.&nbsp; Pored&nbsp; toga&nbsp; ispitani&nbsp; su&nbsp; efekti&nbsp; prirodnih&nbsp; procesa<br />preči&scaron;ćavanja u rečnoj vodi.<br />Nekonvencionalni&nbsp; procesi&nbsp; za&nbsp; preči&scaron;ćavanje&nbsp; otpadnih&nbsp; voda&nbsp; su&nbsp; ispitani&nbsp; pri<br />početnoj&nbsp; koncentraciji&nbsp; supstanci&nbsp; od&nbsp; 0,96&nbsp; &micro;g/l&nbsp; do&nbsp; 2&nbsp; &micro;g/l.&nbsp; Adsorpcija&nbsp; naaktivnom&nbsp; uglju&nbsp; u&nbsp; prahu&nbsp; se&nbsp; pokazala&nbsp; efikasnom&nbsp; (benzofenoni&nbsp; se&nbsp; uklanjaju<br />&gt;84%&nbsp; -&nbsp; &gt;94% u zavisnosti od doze uglja, a kofein je moguće ukloniti i do<br />84%).&nbsp; Koagulacija&nbsp; dozama&nbsp; prirodnog&nbsp; koagulanta&nbsp; od&nbsp; 0,0375&nbsp; ml/l&nbsp; i<br />komercijalnog koagulanta&nbsp; FeCl₃od 4 mg Fe ³⁺ /l se&nbsp; pokazala&nbsp; neefikasnom za<br />sve&nbsp; supstance&nbsp; (&lt;20%).&nbsp; Hibridni&nbsp; PAC/CoA&nbsp; koji&nbsp; je&nbsp; ispitivan&nbsp; sa&nbsp; različitim<br />dozama&nbsp; aktivnog&nbsp; uglja&nbsp; u&nbsp; prahu&nbsp; (5&nbsp; i&nbsp; 20&nbsp; mg/l),&nbsp; prirodnim&nbsp; koagulantom<br />(0,0375 ml/l)&nbsp; ili&nbsp; komercijalnim&nbsp; koagulantom&nbsp; (4 mg Fe ³⁺ /l),&nbsp; pokazao&nbsp; se&nbsp; kao<br />efikasan za uklanjanje BP, BP-3 i CF sa većom dozom&nbsp; uglja A od 20 mg/l (&gt;88%).&nbsp; Hibridni membranski proces&nbsp; PAC/UF je pokazao&nbsp; visoku efikasnost za uklanjanje BP-3 (&gt;68%) i CF (&gt;99,95%) sa dozom uglja od 20 mg/l. Ispitivanjem&nbsp; biodegradacije&nbsp; BP,&nbsp; BP-3&nbsp; i&nbsp; CF&nbsp; primenom&nbsp; laboratorijskog&nbsp; test filtra, postignuta je efikasnost uklanjanja pri koncentraciji od 20 &micro;g/l od&nbsp; 90% do&nbsp; 99%&nbsp; i&nbsp; pokazano&nbsp; da&nbsp; su&nbsp; supstance&nbsp; biodegradabilne.&nbsp; Testovi&nbsp; toksičnosti pokazali&nbsp; su&nbsp; značajno&nbsp; smanjenje&nbsp; ukupne&nbsp; toksičnosti&nbsp; sme&scaron;a&nbsp; tokom laboratorijskog&nbsp; testa,&nbsp; a&nbsp; rezidualna&nbsp; toksičnost&nbsp; u&nbsp; odnosu&nbsp; na&nbsp; <em>D.&nbsp; magna</em>&nbsp; može biti&nbsp; posledica&nbsp; nedetektovanih&nbsp; transformacionih&nbsp; produkata.&nbsp; Transportom supstanci kroz sediment Dunava&nbsp; uočeno je da&nbsp; sediment predstavlja efikasnu barijeru&nbsp; za&nbsp; oba&nbsp; testirana&nbsp; benzofenona,&nbsp; dok&nbsp; CF&nbsp; lako&nbsp; prolazi&nbsp; usled&nbsp; svoje mobilnosti (log Kow -0,07). Eksperimentima fotodegradacije potvrđeno je da degradacija benzofenona UV zračanjem&nbsp; zavisi od prisustva&nbsp; anjona (HCO₃ -, Cl i SO₄^2-)&nbsp; i DOC&nbsp; u vodenom matriksu. Iako primenjeno UV zračenje nije bilo&nbsp; realno&nbsp; za&nbsp; dezinfekciju&nbsp; u&nbsp; tretmanima&nbsp; voda,&nbsp; rezultati&nbsp; su&nbsp; pokazali značaj detaljnije&nbsp; procene&nbsp; kvaliteta&nbsp; vode&nbsp; u&nbsp; slučajevima&nbsp; kada&nbsp; se&nbsp; UV&nbsp; zračenje primenjuje.Za uklanjanje odabranih supstanci iz rečne vode ispitani su&nbsp; konvencionalni procesi&nbsp; (zasebno&nbsp; adsorpcija&nbsp; na&nbsp; aktivnom&nbsp; uglju&nbsp; u&nbsp; prahu&nbsp; i&nbsp; koagulacija komercijalnim&nbsp; koagulantom,&nbsp; BOPAC &reg; )&nbsp; i&nbsp; hibridni&nbsp; ili&nbsp; nekonvencionalni<br />procesi&nbsp; adsorpcije/koagulacije&nbsp; (PAC/CoA),&nbsp; adsorpcije/ultrafiltracije (PAC/UF) kao i koagulacije/ultrafiltracije (CoA/UF). Tokom ispitivanja PAC/CoA sa ugljem B (2 mg/l) i BOPAC &reg; (2 mg Al ³⁺ /l) u određenim&nbsp; procesnim&nbsp; kombinacijama,&nbsp; (tokom&nbsp; sukcesivnog&nbsp; dodavanja&nbsp; prvo uglja&nbsp; B,&nbsp; a&nbsp; zatim&nbsp; koagulanta)&nbsp; uočene&nbsp; su&nbsp; specifičnosti&nbsp; za&nbsp; BP,&nbsp; efikasnost uklanjanja BP je iznosila 92%. U slučaju doziranja prvo koagulanta, a zatim uglja&nbsp; B&nbsp; i&nbsp; tokom&nbsp; simultanog&nbsp; doziranja&nbsp; koagulanta&nbsp; i&nbsp; uglja&nbsp; B,&nbsp; efikasnosti&nbsp; su iznosile&nbsp; 23&nbsp; i&nbsp; 20%,&nbsp; redom.&nbsp; To&nbsp; je&nbsp; verovatno&nbsp; posledica&nbsp; kompeticije&nbsp; iliblokiranja pora&nbsp; uglja&nbsp; POM iz rečne vode.&nbsp; BP-3 se efikasno uklanjao tokom svih procesnih kombinacija sa ugljem B (87-93%), dok je za CF efikasnost<br />uklanjanja iznosila&nbsp; od 0-12%.&nbsp; Hibridni procesi su se pokazali efikasniji pri<br />primeni uglja C. U slučaju BP efikasnost je iznosila 81-90% i za CF 17-27% ,dok&nbsp; je&nbsp; za&nbsp; BP-3&nbsp; efikasnost&nbsp; iznosila&nbsp; od&nbsp; 71%&nbsp; do&nbsp; 96%.&nbsp; Hibridni&nbsp; membranski procesi&nbsp; PAC/UF&nbsp; i&nbsp; CoA/UF&nbsp; u&nbsp; obradi&nbsp; rečne&nbsp; vode&nbsp; efikasni&nbsp; su&nbsp; u&nbsp; uklanjanju supstanci&nbsp; sa&nbsp; visokim&nbsp; log&nbsp; Kow.&nbsp; Benzofenoni&nbsp; su&nbsp; u&nbsp; hibridnim&nbsp; membranskim procesima&nbsp; uklonjeni&nbsp; od&nbsp; 69%-96% iz rečne&nbsp; vode, dok su za kofein utvrđeni promenljivi rezultati i potreba za daljim istraživanjima.</p> / <p>Benzophenones and caffeine are ubiquitous&nbsp; in wastewaters&nbsp; and in surface&nbsp; waters,&nbsp; in&nbsp; concentrations&nbsp; that&nbsp; vary&nbsp; from&nbsp; ng/L&nbsp; to&nbsp; mg/L. Benzophenones&nbsp; are&nbsp; used&nbsp; as:&nbsp; smell&nbsp; and&nbsp; flavor&nbsp; enhancers,&nbsp; perfume&nbsp; fixers, plastic additives, cleaning agents, as well as in the pesticide manufacturing processes.&nbsp; Their&nbsp; UV-resistant&nbsp; properties,&nbsp; makes&nbsp; benzophenones&nbsp; a&nbsp; suitable packaging component&nbsp; &ndash;&nbsp; to&nbsp; prevent UV light from damaging the odor or the color of the product. Similarly, benzophenone-3 is most commonly used in the&nbsp; cosmetics&nbsp; industry;&nbsp; as&nbsp; a&nbsp; UV&nbsp; filter&nbsp; agent&nbsp; in&nbsp; sunscreens,&nbsp; body&nbsp; lotions, shampoos, paints and hair sprays.&nbsp; On the other hand, caffeine is prevalent in food-,&nbsp; pharmaceutical-&nbsp; and&nbsp; cosmetics-manufacturing.&nbsp; However, benzophenones&nbsp; and&nbsp; caffeine&nbsp; have&nbsp; significantly&nbsp; different&nbsp; log&nbsp; Kow&nbsp; values. Log Kow values for benzophenone and benzophenone-3 are 3.18 and 3.79,respectively, while for caffeine log Kow is&nbsp; -0.07.&nbsp; Due to the lack of data on the&nbsp; content&nbsp; of&nbsp; selected&nbsp; benzophenones,&nbsp; (benzophenone&nbsp; (BP)&nbsp; and benzophenone-3&nbsp; (BP-3))&nbsp; and&nbsp; caffeine&nbsp; (CF)&nbsp; in&nbsp; different&nbsp; types&nbsp; of&nbsp; water (primarily in local wastewater and&nbsp; river water) and their behavior in water treatments, tests were&nbsp; carried out: a) in the effluent of a typical wastewater treatment&nbsp; plant (WWTP);&nbsp; b) and&nbsp; in&nbsp; the river Danube.&nbsp; In case of the WWTP effluent, the presence of all three compounds was detected in the following ranges: 0.112 &mu;g/L to 0.146 &mu;g/L for BP, 0.00718 &mu;g/L to 0.42 &mu;g/L for BP-3,&nbsp; and&nbsp; 0.2&nbsp; &mu;g/L&nbsp; to&nbsp; 12&nbsp; &mu;g/L&nbsp; for&nbsp; CF.&nbsp; With&nbsp; respect&nbsp; to&nbsp; the&nbsp; Danube&nbsp; river,&nbsp; the highest&nbsp; detected&nbsp; concentration&nbsp; for&nbsp; BP&nbsp; was&nbsp; 0.95 &mu;g/L,&nbsp; for&nbsp; BP-3&nbsp; was 0.62 &mu;g/L,&nbsp; while&nbsp; CF&nbsp; in&nbsp; Danube&nbsp; river&nbsp; sample&nbsp; was&nbsp; measured&nbsp; in&nbsp; only&nbsp; one sample, resulting in a concentration of 0.7 &mu;g/L. In addition, this&nbsp; work has investigated&nbsp; the&nbsp; efficacy&nbsp; of&nbsp; several&nbsp; treatment&nbsp; processes:&nbsp; unconventional processes&nbsp; in&nbsp; the&nbsp; WWTP&nbsp; effluent&nbsp; treatment&nbsp; (adsorption,&nbsp; coagulation, PAC/CoA, PAC/UF);&nbsp; as well as the&nbsp; conventional (adsorption, coagulation) and&nbsp; unconventional&nbsp; processes&nbsp; (PAC/CoA,&nbsp; PAC/UF,&nbsp; CoA/UF)&nbsp; in&nbsp; the treatment&nbsp; of&nbsp; river&nbsp; waters.&nbsp; Furthermore,&nbsp; the&nbsp; effects&nbsp; of&nbsp; natural&nbsp; purification processes&nbsp; in&nbsp; river&nbsp; water&nbsp; had&nbsp; also&nbsp; been&nbsp; examined&nbsp; within&nbsp; the&nbsp; scope&nbsp; of&nbsp; this research.Unconventional&nbsp; wastewater&nbsp; treatment&nbsp; processes&nbsp; were&nbsp; investigated&nbsp; at&nbsp; initial concentrations&nbsp; of&nbsp; selected substances&nbsp; that ranged&nbsp; from 0.96 &mu;g/L to 2 &mu;g/L. Adsorption&nbsp; on&nbsp; powder&nbsp; activated&nbsp; carbon&nbsp; was&nbsp; effective&nbsp; for&nbsp; removal&nbsp; of benzophenones&nbsp; (&gt; 84%&nbsp; -&gt; 94%)&nbsp; and caffeine&nbsp; (84%),&nbsp; depending on the&nbsp; dose of PAC A. Coagulation with doses of&nbsp; natural coagulant of 0.0375 mL/L&nbsp; and commercial&nbsp; coagulant&nbsp; FeCl 3 of&nbsp; 4&nbsp; mg&nbsp; Fe 3+ /L&nbsp; was&nbsp; ineffective&nbsp; for&nbsp; all substances&nbsp; (&lt;20%).&nbsp; Hybrid&nbsp; PAC/CoA&nbsp; process,&nbsp; investigated&nbsp; with&nbsp; different doses&nbsp; of&nbsp; PAC&nbsp; A&nbsp; (5&nbsp; and&nbsp; 20&nbsp; mg/L),&nbsp; natural&nbsp; coagulant&nbsp; (0.0375&nbsp; mL/L)&nbsp; or commercial coagulant (4 mg Fe 3+ /L), proved to be effective for&nbsp; the removal of BP, BP-3 and CF at a higher PAC A dose of 20 mg/L (&gt; 88%). The hybrid membrane process PAC/UF proved to be highly effective in the&nbsp; removal of BP-3 (&gt; 68%) and CF (&gt; 99.95%) with&nbsp; 20 mg/L&nbsp; of&nbsp; PAC A.&nbsp; Biodegradation of BP, BP-3 and CF had been confirmed in Danube river water sample using a&nbsp; laboratory&nbsp; test&nbsp; filter&nbsp; filled&nbsp; with&nbsp; inert&nbsp; material.&nbsp; The&nbsp; removal&nbsp; efficacy&nbsp; was 90-99%&nbsp; at&nbsp; a&nbsp; concentration&nbsp; of&nbsp; 20&nbsp; &mu;g/L.&nbsp; Toxicity&nbsp; tests&nbsp; showed&nbsp; significant reduction in total toxicity of the mixture during the&nbsp; course of the&nbsp; laboratory test,&nbsp; whereas&nbsp; the&nbsp; residual&nbsp; toxicity&nbsp; in&nbsp; relation&nbsp; to&nbsp; D.&nbsp; magna&nbsp; may&nbsp; be&nbsp; due&nbsp; to undetected transformation products. Transportation of the substances through the&nbsp; Danube&nbsp; sediment,&nbsp; indicated that sediment&nbsp; acts as&nbsp; an&nbsp; effective barrier for both tested benzophenones, while&nbsp; this is not&nbsp; the&nbsp; case with&nbsp; CF.&nbsp; Its mobility (log Kow&nbsp; -0.07) allows CF to pass through the sediment.&nbsp; Photodegradation experiments have confirmed that&nbsp; BP&nbsp; degradation&nbsp; occurs due to&nbsp; the presence of&nbsp; anions&nbsp; (HCO 3-, Cl&nbsp; 2-) and DOC in the aqueous matrix. Although the applied UV radiation was&nbsp; not a realistic representation of disinfection in conventional water treatments, the results showed the importance of a more detailed&nbsp; assessment&nbsp; of&nbsp; the&nbsp; water&nbsp; quality&nbsp; in&nbsp; cases&nbsp; where&nbsp; UV&nbsp; radiation&nbsp; is applied.&nbsp; Herien&nbsp; investigated&nbsp; are&nbsp; also&nbsp; conventional&nbsp; processes&nbsp; (separately adsorption on PAC,&nbsp; and coagulation&nbsp; with commercial coagulant -&nbsp; BOPAC &reg; ) and hybrid or unconventional&nbsp; adsorption/coagulation&nbsp; processes (PAC/CoA), adsorption/ultrafiltration (PAC/UF) and coagulation/ultrafiltration (CoA/UF) for the&nbsp; removal of the selected substances from river water.The efficiency of BP&nbsp; removal&nbsp; via&nbsp; PAC/CoA&nbsp; with&nbsp; PAC&nbsp; B&nbsp; (2&nbsp; mg/L)&nbsp; and&nbsp; BOPAC &reg; (2 mg Al 3+ /L)&nbsp; observed&nbsp; specificity&nbsp; of&nbsp; removal&nbsp; of&nbsp; BP&nbsp; in&nbsp; certain&nbsp; process combinations, such as successive addition of first PAC B and then coagulant. The efficacy of such BP removal was 92%. In case of the initial coagulant dosing, then PAC B, and in the case of simultaneous dosage of coagulant anPAC&nbsp; B,&nbsp; efficacy&nbsp; were:&nbsp; 23%&nbsp; and&nbsp; 20%,&nbsp; respectively.&nbsp; Such&nbsp; outcome&nbsp; is probably&nbsp; a&nbsp; result&nbsp; of&nbsp; the&nbsp; competition/blocking&nbsp; of&nbsp; natural&nbsp; organic&nbsp; matter&nbsp; in river&nbsp; water.&nbsp; BP-3&nbsp; was&nbsp; efficiently&nbsp; removed&nbsp; during&nbsp; all&nbsp; process&nbsp; combinations with&nbsp; PAC&nbsp; B&nbsp; (87-93%),&nbsp; while&nbsp; the&nbsp; efficiency&nbsp; of&nbsp; CF&nbsp; ranged&nbsp; from&nbsp; 0-12%.&nbsp; In general, hybrid process proved to be more efficient in case of PAC C. For BP and&nbsp; CF,&nbsp; the&nbsp; efficacy&nbsp; of&nbsp; removal&nbsp; amounted&nbsp; to&nbsp; 81-90%&nbsp; and&nbsp; 17-27%, respectively, wheareas the efficiency of BP-3 removal was found to be in the range&nbsp; of&nbsp; 71-96%.&nbsp; For&nbsp; the&nbsp; treatment&nbsp; of&nbsp; river&nbsp; water,&nbsp; hybrid&nbsp; membrane processes PAC/UF and&nbsp; CoA/UF are effective in the removal of&nbsp; substances with&nbsp; high&nbsp; log&nbsp; Kow.&nbsp; Benzophenones&nbsp; were&nbsp; removed&nbsp; from&nbsp; hybrid&nbsp; membrane processes&nbsp; by&nbsp; 69%-96% from river water, while caffeine was found to have less consistent results and requires further research.</p>

It is fundamental to investigate the biodegradability of chemicals and their potential (eco)toxicological effects under near-environmental conditions in order to identify and thereby avoid potential risks to humans, animals and the environment in the event of their release. Established as a policy object at the European level, the risks, which are posed by anthropogenic pollution, ideally need to be reduced to a minimum, if not eliminated completely, in the near future. To achieve this goal, an assessment of chemicals, based on international consensus, is required, which builds on the results of standardized experiments and is constantly supplemented by computer-based approaches. Establishing structure-property relationships is one way to immediately classify organic trace substances as ‘degradable’, or ‘potentially persistent’, as well as as hormonally ‘active’ or ‘inactive’. The extent to which these relationships are applicable to the substance group of benzophenone-type UV filters was investigated in this work. Some derivatives, which only differ in the type and position of their substituents on the aromatic rings, are suspected of acting as endocrine disruptors. Despite the high probability of them being released into the environment, and the toxicologically relevant properties, there are no mechanistic degradation studies so far that take enough derivatives into consideration to discuss the substitution pattern as a possible influential factor. To close the identified gaps, experiments on primary as well as ultimate degradation were carried out with up to ten different benzophenones, changing various parameters and adapting the experimental setup. Studies on the complete mineralizability, compliant with the standardized OECD Guideline No. 301F, showed that the respective substitution pattern is a decisive factor, while the mere presence of certain functional groups plays a minor role. To yield additional information on the time-dependent formation of primary degradation products, an LC-MS/MS method was developed that served to quantify benzophenones in various environmental matrices during a monitoring campaign, in addition to tracking primary degradation at the laboratory scale. The detection of 4-hydroxybenzophenone, which meets the structural criteria for multi-hormonal effects and was identified as a microbial degradation product of benzophenone, confirmed that the formation of transformation products needs to be given greater consideration in relation to toxicological issues. On this evidence, the structure-dependent endocrine effects of benzophenone-type UV filters, the transformation product 4-hydroxybenzophenone, and three other degradation products were determined using recombinant yeast-based reporter gene assays. Hydroxyl groups are the prevalent substituents of benzophenone-type UV filters, and the ruling structural elements, which influence microbial biodegradation and endocrine activity. Their investigation revealed a new fundamental but unexpected relationship: Primary degradation can slow down further degradation through the incorporation of hydroxyl groups. This simultaneously increases the risk of a formation of estrogen-active transformation products. This aspect underlines the need to include the occurrence of transformation products, especially under realistic conditions, in the overall risk assessment of chemicals. In this context, the application of quantitative structure-activity relationships (QSAR) plays a crucial role and, the suitability thereof was verified in this work – focusing on benzophenones. The empirically proven relationship between substitution pattern and degradability helps to improve the reliability of QSAR models for benzophenones as well as for structurally similar compounds, and forms the basis for further studies of this specific relationship at the enzymatic level.:DECLARATION OF CONFORMITY DECLARATION OF INDEPENDENT WORK PREFACE ACKNOWLEDGMENT KURZFASSUNG ABSTRACT LIST OF ABBREVIATIONS AND ACRONYMS 1 CONTEXTUAL FRAMEWORK AND OBJECTIVES 2 STATE OF KNOWLEDGE ABOUT THE BIODEGRADATION OF BENZOPHENONES 2.1 INTRODUCTION 2.2 ENTRY PATHS INTO THE ENVIRONMENT AND HAZARDOUS EFFECTS 2.2.1 Environmental occurrence and possible routes of discharge 2.2.2 (Eco)toxicity and endocrine disrupting properties 2.3 BIODEGRADATION 2.3.1 Aerobic biotransformation 2.3.2 Anoxic/anaerobic biotransformation 2.3.3 Transformation mediated through fungi and higher organisms 2.4 PHOTOLYTIC TRANSFORMATION 2.5 CONCLUSIONS 3 TRACE ANALYSIS IN ENVIRONMENTAL SAMPLES AND THE ENDOCRINE EFFECTS 3.1 INTRODUCTION 3.2 MATERIAL AND METHODS 3.2.1 Chemicals and materials 3.2.2 LC-MS/MS method development 3.2.2.1 MS parameters 3.2.2.2 LC parameters 3.2.2.3 Sample preparation 3.2.2.4 Validation 3.2.2.5 Application of the method to environmental monitoring 3.2.3 Biodegradation 3.2.4 Yeast-based reporter gene assays 3.3 RESULTS AND DISCUSSION 3.3.1 LC-MS/MS method development 3.3.1.1 Sample preparation 3.3.1.2 Validation 3.3.1.3 Application of the method for environmental samples 3.3.2 Biodegradation 3.3.3 Endocrine activity 3.3.3.1 Estrogenic and antiestrogenic activities 3.3.3.2 Estrogenic activity during biotransformation 3.3.3.3 Androgenic and antiandrogenic activities 3.4 CONCLUSION 4 PRIMARY AND ULTIMATE DEGRADATION 4.1 INTRODUCTION 4.2 MATERIAL AND METHODS 4.2.1 Chemicals and materials 4.2.2 Primary degradation 4.2.2.1 Abiotic river water 4.2.2.2 Biotic river water 4.2.2.3 Suboxic river water 4.2.2.4 River water amended with mineral solution 4.2.3 Ready biodegradability 4.2.4 Column experiments 4.2.5 Docking studies 4.2.6 LC-MS/MS Analysis 4.3 RESULTS AND DISCUSSION 4.3.1 Primary degradation 4.3.1.1 Abiotic river water 4.3.1.2 Biotic river water 4.3.1.3 Suboxic river water 4.3.1.4 River water amended with mineral solution 4.3.2 Ready biodegradability 4.3.3 Column experiments 4.3.3.1 Breakthrough curves and pretests 4.3.3.2 Removal tests 4.3.4 Structure-biodegradability relationships 4.4 CONCLUSIONS 5 SYNTHESIS 5.1 SUMMARIZING DISCUSSION 5.2 COMPARISON TO IN SILICO RESULTS 5.2.1 Biodegradability 5.2.2 Estrogenicity 5.3 CONCLUSION 6 APPENDIX 6.1 APPENDIX A 6.2 APPENDIX B 6.3 APPENDIX C 6.4 APPENDIX D 7 REFERENCES

A crescente demanda por novos compostos químicos sintéticos para atender as necessidades médicas, agrícolas e industriais da população resultou no surgimento de novos contaminantes, denominados emergentes. Com a intensa utilização destes compostos em diversos produtos e o consequente aumento da concentração destes no meio ambiente, a população passou a estar exposta e sujeita aos seus possíveis efeitos deletérios. Os disruptores endócrinos fazem parte do grupo de contaminantes emergentes que tem a capacidade de interferir na ação natural dos hormônios por diferentes mecanismos, podendo agravar o quadro de doenças pré-existentes e causar diversos outros danos à saúde humana. Apesar de serem largamente utilizados na vida cotidiana, a regulamentação do uso desses compostos ainda é quase inexistente, aumentando a preocupação quanto à sua segurança. Comumente, os estudos de biomonitoramento humano para avaliar a exposição da população em geral são realizados utilizando amostras de sangue e urina. Neste sentido, o presente estudo teve como objetivo desenvolver um método alternativo para determinação simultânea de 17 compostos classificados como disruptores endócrinos: bisfenóis, parabenos, benzofenonas e triclocarban em saliva, empregando a microextração líquido-liquido dispersiva (DLLME) no preparo da amostra e cromatografia líquida de alta eficiência acoplada à espectrometria de massas (LC-MS/MS) para a determinação. Os seguintes parâmetros foram avaliados na otimização da DLLME: volume e tipo de solvente extrator e dispersor, força iônica, pH e agitação. Após a otimização, o processo de extração foi realizado adicionando-se 500 ?L de água deionizada à 500 ?L da amostra de saliva. Os solventes extrator e dispersor selecionados foram triclorometano e acetona, respectivamente (volume de 2 mL da mistura na proporção 1:3). Foi adicionada a etapa de agitação manual por dez segundos. As curvas de calibração de todos os analitos apresentaram linearidade, com coeficiente de correlação superiores a 0,99 no intervalo de concentração de 1-20 ng mL-1. O coeficiente de variação (CV) intra e interdias foram inferiores a 20% para o primeiro ponto da faixa linear e inferiores a 15% para as demais concentrações. O erro padrão relativo intra e interdias foram inferiores a 20% para o primeiro ponto da faixa linear e inferiores a 15% nas demais concentrações. Os limites de detecção (LOD) e de quantificação (LOQ) encontrados variaram de 0,01 - 0,15 ng mL-1 e 0,05 - 0,40 ng mL-1, respectivamente. Para avaliar a aplicabilidade do método, dez amostras de saliva foram analisadas e apresentaram concentrações detectáveis de bisfenol S (BPS), bisfenol AF (BPAF) e propilparabeno (PrP) ( <LOQ). O bisfenol A (BPA) e a benzofenona-3 (BP3) foram encontrados em concentrações que variaram entre 1,01-3,14 e 1,00-2,50 ng mL-1, respectivamente. O metilparabeno (MeP) foi detectado em todas as amostras, atingindo, nos níveis quantificáveis, a concentração de 17,8 ng mL-1. Portanto, o método aqui proposto é uma alternativa simples e rápida para estudos de biomonitoramento humano, capaz de determinar 17 analitos multi-classes simultaneamente com uso de baixo volume de solventes. / The growing demand of new synthetic chemical compounds to attend the medical, agricultural and industrial needs of the population has resulted in the emergence of new contaminants, known as emerging contaminants. The presence of these contaminants in several products, and its consequent concentration increase in the environment, exposed the population and subject them to possible deleterious effects. Endocrine disruptors are a group of these contaminants that have the ability to interfere at the natural action of hormones by different mechanisms, wich can worsen preexistent diseases and cause other damages to humam health. Despite the widely utilization of these compounds in everyday life, regulation of its use is almost non-existent, raising concerns about their safety. Mostly human biomonitoring studies to assess the exposure of the population are performed in urine and blood samples. In these sense, the present study aimed to develop an alternative method for simultaneous determination of 17 endocrine disrupting compounds: bisphenols, parabens, benzophenones and triclocarban in saliva, using dispersive liquid-liquid microextraction (DLLME) at sample preparation and high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) for determination. The evaluated parameters in the optimization of DLLME were: volume and type of extraction and disperser solvents, ionic strength, pH and agitation. After the optimization, the extraction procedure was performed by adding 500 ?L of deionized water to 500 ?L of saliva sample. The extraction and disperser solvents selected were trichloromethane and acetone, respectively (2 mL of the mixture in 1:3 ratio). The manual agitation for ten seconds. The matrix-matched calibration curves of all analytes were linear, with correlation coefficients higher than 0.99 in the range level of 1 - 20 ng mL-1. The intra and interday coefficient of variation (CV) was less than 20% for the first point of the linear range and less than 15% for the other concentrations. The intra and interday relative standard deviation (RSD) was less than 20% for the first point of the linear range and less than 15% for the other concentrations. The limits of detection (LOD) and quantification (LOQ) ranged from 0,01 - 0,15 ng mL-1 and 0,05 - 0,4 ng mL-1, respectively. To evaluate the applicability of the method, ten saliva samples were analyzed, showing detectable concentrations (<LOQ) of bisphenol S (BPS), bisphenol AF (BPAF) and propylparaben (PrP). Bisphenol A (BPA) and benzophenone-3 (BP3) were found in ranging concentrations from 1,01 - 3,14 and 1,00 - 2,50 ng mL-1, respectively. Methylparaben (MeP) was detected in all samples, reaching, at the quantifiable levels, the concentration of 17,8 ng mL-1. Thus, the proposed method is a simple and fast alternative for human biomonitoring studies, capable of determining 17 multi-class analytes simultaneously using low volume of solvent.

Os compostos lipofílicos da própolis vermelha brasileira (PVB) têm recebido atenção especial devido a interessantes relatos referentes às suas atividades biológicas. Neste contexto, este estudo teve três etapas: a primeira objetivou investigar a atividade do extrato bruto etanólico da PVB e respectivas frações (obtidas com solventes de polaridade crescente, por meio de maceração em temperatura ambiente) contra cepas de Candida não-albicans (CNA) - C. krusei, C. glabrata, C. tropicalis e C. parapsilosis. A concentração inibidora mínima (CIM) foi determinada pelo método de microdiluição em caldo, com concentrações variando entre 1,9 a 500 μg/mL. Dentre as frações testadas, a fração hexânica (HEX) apresentou maior potencial antifúngico, alcançando valor de CIM de 1,95 μg/mL contra espécies de C. parapsilosis. Para cepas de C. glabrata, C. krusei e C. tropicalis, os valores de CIM obtidos foram variáveis (1,95-250 μg/mL). Ensaio colorimétrico de MTT foi utilizado para confirmar o dano celular e os resultados variaram de 80,66 a 94,44%, com extensa morte celular causada pela HEX, incluindo efeitos contra cepas resistentes de CNA, principalmente C. glabrata e C. parapsilosis. Esta potencial capacidade antifúngica está relacionada com compostos lipofílicos, provavalmente benzofenonas polipreniladas (BPPs), anteriormente descritas para PVB. A segunda etapa teve como objetivo avaliar a composição química do extrato hexânico da PVB (HEXred) por CLUE-DAD-EM. A investigação química resultou, principalmente, na identificação de BPPs (oblongifolina A, gutiferona E e/ou xantochimol). Após, um método de CLAE-UV isocrático foi validado para a determinação do teor total de BPPs (a 260 nm) expresso como garcinol, um diasterorisômero da gutiferona E disponível comercialmente. O método mostrou ser específico, exato, preciso e linear (0,1 a 10 μg/mL) para a determinação de BPPS na HEXred e na nanoemulsão (NE) contendo HEXred, bem como em amostras de pele e mucosa suínas, após estudos de permeação/retenção. O efeito matriz foi determinado para todas as matrizes complexas, demonstrando baixo efeito durante a análise. A estabilidade do método foi verificada por meio da exposição da HEXred às condições de estresse ácida, alcalina, oxidativa e térmica. Não houve interferência dos produtos de degradação durante a análise, indicando que o método analítico/bioanalítico proposto provou ser simples e confiável para a determinação de BPPs na presença de diferentes matrizes. Como terceiro passo nós buscamos otimizar a incorporação de BPPs em NE destinada ao tratamento de infecções fúngicas mucocutâneas. A otimização da NE foi realizada por meio de experimento de Box-Behnken, que permitiu avaliar simultaneamente a influência das concentrações do fosfolipídeo da lecitina de gema de ovo, do lípido catiónico DOTAP e das BPPs nas propriedades físico-químicas da NE, bem como na eficiência de associação (EA) das BPPs. Utilizando o software Mini-Tab®, a formulação ótima foi selecionada com base no menor tamanho de gotícula e maiores potencial zeta e eficiência de associação, exibindo um tamanho médio de 140,56 ± 5,22 nm, potencial zeta de + 60,72 ± 3,07 e 99,55 ± 1,09% de EA. Células de difusão do tipo Franz foram usadas para avaliar a distribuição das BPPs através da pele e mucosa suínas, sendo encontradas BPPs nas camadas de ambos os tecidos (principalmente na derme). Uma maior quantidade de BPPs (até 3 vezes) foi detectada na pele e mucosa lesadas o que demonstra o efeito da integridade do tecido na distribuição das BPPs, como sugerido por imagens de microscopia confocal de fluorescência. As BPPs foram detectadas no fluido receptor apenas quando a mucosa esofágica foi lesada. A atividade antifúngica das formulações foi investigada contra espécies de CNA - C. krusei, C. glabrata, C. tropicalis e C. parapsilosis. Os valores de CIM variaram de 0,654 a 2,617 μg/mL, com dano celular superior a 78% como verificado por ensaio de MTT. Tais resultados sugerem que a NE otimizada possui potencial promissor para ser utilizada topicamente para o tratamento de infecções fúngicas mucocutâneas causadas por espécies de CNA. / Lipophilic compounds of Brazilian red propolis (BRP) have received increasing attention due to some interesting findings regarding their biological activities. This study had three steps: first we aimed to investigate the activity of BRP crude ethanolic extract and their fractions (obtained with increasing polarity solvents, through maceration at room temperature) against non-albicans Candida (NAC) strains. Minimal inhibitory concentration (MIC) was determined by the broth microdilution method, with concentrations ranging from 1.9 to 500 μg/mL. Among the tested fractions, n-hexane fraction (HEX) showed higher antifungal potential, achieving MIC values of 1.95 μg/mL against C. parapsilosis strains. On C. glabrata, C. krusei and C. tropicalis strains, variable MIC values were obtained (1.95 to 250 μg/mL). MTT colorimetric assay was employed to confirm the cell damage and the results ranged from 80.66 to 94.44%, with extensive cell death caused by HEX, including the effects against NAC resistant strains, mainly C. glabrata and C. parapsilosis. This potential antifungal capacity showed by HEX is related to the lipophilic compounds, probably polyprenylated benzophenones (PPBs), previous described for BRP. In the second step we aimed to evaluate the chemical composition of BRP n-hexane extract (HEXred) by UPLC-PDA-MS. Chemical investigation mainly resulted in the identification of PPBs in this extract, named oblongifolin A, guttiferone E, and/or xanthochymol. After that, an isocratic HPLC-UV method was validated for the determination of total content of PPBs (at 260 nm) expressed as garcinol, a commercially available guttiferone E diastereoisomer. The method showed to be specific, precise, accurate, and linear (0.1 to 10 μg/mL) for the determination of PPBs in HEXred, BRP-loaded nanoemulsions (NE), as well as, in porcine skin and mucosa samples after permeation/retention studies. The matrix effect was determined for all complex matrices, demonstrating low effect during the analysis. The stability-indicating method was verified by submitting HEXred to acidic, alkaline, oxidative, and thermal stress conditions. No interference of degradation products was detected during analysis, indicating that the proposed analytical/bioanalytical method proved to be simple and reliable for the determination of PPBs in the presence of different matrices. As third step we aimed to optimize the incorporation of PPBs into NE intended for the treatment of mucocutaneous fungal infections. The optimization of NE was performed by means of a Box-Behnken Design, which allowed evaluating simultaneously the influence of the phospholipid egg-lecithin, the cationic lipid DOTAP and PPBs concentrations on the physicochemical properties of NE, as well as on the association efficiency (AE) of PPBs. By using the Mini Tab® software, the optimal formulation was selected based on the smallest droplet size and highest zeta potential and AE, exhibited a mean average size of 140.56±5.22 nm, zeta potential of +60.72±3.07 and AE of 99.55±1.09%. Franz-type diffusion cells were used to evaluate PPBs distribution through porcine skin and mucosa being PPBs found in both mucosa and skin layers (mainly in the dermis). A higher amount of PPBs (up to 3-fold) was detected in impaired skin and mucosa demonstrating the effect of the integrity of the tissue on PPBs distribution, as suggested by confocal fluorescence microscopy images. PPBs were detected in the receptor fluid only when esophageal mucosa was impaired. The antifungal activity of the formulations was investigated against NAC species – C. krusei, C. glabrata, C. tropicalis and C. parapsilosis. MIC values varied from 0.654 to 2.617 μg/mL, with cell damage higher than 78 % as verified by MTT assay. Such results suggest that the optimized NE have promising potential to be used topically for the treatment of mucocutaneous fungal infections caused by NAC strains.