Dietary flavonoids are ubiquitous and are marketed as supplements. Characterized as antioxidants, they offer protection against a number of degenerative diseases. Flavonoid mechanics involve free radical scavenging, metal chelation, and substrate association. The skeletal structure of flavonoids is a fused ring system modified by hydroxyl, sugar, and carbohydrate additions. Flavone is a structurally simple flavonoid. Quercetin and its glycosidic analog rutin are complex structures. Using a DNA oxidation/cleavage assay, flavone reduces DNA nicking by 91%. Depending on the solvent system used, quercetin can either increase or decrease DNA oxidation. Rutin exhibits neither pro- nor antioxidant activity. The molecular interactions responsible for these results are defined for flavone. 1) Flavone intercalates into DNA and saturates DNA at a 1/3.5 flavone:DNA molar ratio. 3) Flavone reduces iron-dependent DNA oxidation. 4) Flavone interacts with quercetin to enhance DNA protection. These results characterize the primary activities of a simple flavonoid.

Les maladies tropicales provoquées par des parasites protozoaires tels que Trypanosoma brucei, Plasmodium falciparum et Leishmania donovani, infectent des milliards d'individus dans le monde et en tuent des millions chaque année. Actuellement, les phénomènes de résistance face aux thérapies actuelles utilisées pour traiter ces maladies dites " négligées " deviennent inquiétants et problématiques. Par conséquent, la découverte de nouvelles classes de molécules bioactives antiparasitaires est primordiale.C'est dans ce contexte que s'inscrit ce travail de thèse. La cissampeloflavone est un dimère chalcone-flavone isolé en 2003 d'une plante vénézuélienne, Cissampelos pareira. Cette molécule a démontré une bonne activité contre T. brucei (CI50 = 1 µM). Par ailleurs, des études de modélisation moléculaire ont prédit que son dérivé 4-désoxycissampeloflavone possèderait une bonne affinité pour une enzyme essentielle à la survie du parasite. Pour ces raisons, nous avons entrepris la synthèse totale de ces deux molécules originales jamais réalisée à ce jour.Des analogues simplifiés ont d'abord été synthétisés afin de mettre au point le schéma réactionnel pour former la cissampeloflavone et la 4-désoxycissampeloflavone. Ces composés ont pour base commune le noyau benzofurane qui porte soit la " partie chalcone " soit la " partie flavone " de ces dimères. Les deux synthèses totales ont ensuite été entreprises.Ce travail de thèse a notamment permis la création d'une librairie d'analogues benzofuranes polysubstitués, la découverte d'une réaction de méthylénation originale et la formation de nouveaux dérivés furanoflavones. La plupart ont été évalués sur T. brucei, P. falciparum et L. donovani. Plusieurs d'entre eux ont présenté une activité trypanocide intéressante et prometteuse.

München, Techn. Univ., Diss., 2004.

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-05-02T11:53:47Z No. of bitstreams: 1 julianaviciniflorentino.pdf: 13579179 bytes, checksum: bacc80aab9aabc49f5ee8f5edbdcc799 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-05-09T12:00:54Z (GMT) No. of bitstreams: 1 julianaviciniflorentino.pdf: 13579179 bytes, checksum: bacc80aab9aabc49f5ee8f5edbdcc799 (MD5) / Made available in DSpace on 2018-05-09T12:00:54Z (GMT). No. of bitstreams: 1 julianaviciniflorentino.pdf: 13579179 bytes, checksum: bacc80aab9aabc49f5ee8f5edbdcc799 (MD5) Previous issue date: 2018-02-22 / A esquistossomose é uma doença parasitária mais comum em áreas tropicais e subtropicais e é uma das doenças mais negligenciadas em todo o mundo. Devido ao fato de até o momento apenas um fármaco (PZQ) ser utilizado no tratamento da esquistossomose e como consequências, diversas dificuldades já estão aparecendo como resistência a sua utilização, não prevenção contra reinfecção e nem contra formas imaturas do parasito, a busca por alternativas tem despertado bastante interesse. Desta forma, neste trabalho foram preparados vinte e oito compostos sendo quatorze chalconas e quatorze flavonas sendo apenas duas flavonas inéditas. As chalconas foram obtidas através da reação de condensação de Claisen-Schimdt, pela reação de cinco aldeídos alquilados e nove aldeídos comerciais com a 2-hidroxiacetofenona. As quatorze flavonas correspondentes foram obtidas através da reação de ciclização oxidativa das chalconas na presença de I2 e DMSO. Todas as chalconas foram obtidas em sua configuração E e todos os compostos sintetizados foram caracterizados por RMN de ¹H e ¹³C. Quatro flavonas foram testadas com relação a sua atividade esquistossomicida in vitro e mostraram potencial como antiparasitários. Além disso, as flavonas foram testadas com relação a sua atividade enzimática frente a enzima ATP-difosfohidrolase e destas, quatro mostraram um potencial interessante frente a inibição desta enzima. / Schistosomiasis is a common parasitic disease in tropical and subtropical areas and it is one of the most neglected diseases in the world. The search for alternatives has aroused a lot of interest since, so far, only one drug (PZQ) is used in the treatment of schistosomiasis and because of this, several consequences are appearing as resistance to its use and non-prevention against reinfection or against immature forms of the parasite. Therefore, in this work twenty-eight compounds were prepared, fourteen chalcones and fourteen flavones which only two flavones are unpublished. Chalcones were obtained by reaction of five alkyl aldehydes and nine commercial aldehydes with 2-hydroxyacetophenone via the Claisen-Schimdt condensation reaction. The corresponding fourteen flavones were obtained through the oxidative cyclization reaction of chalcones in the presence of I2 and DMSO. All chalcones were obtained in their E configuration and all compounds synthesized were characterized by ¹H and ¹³C NMR. Also, the infrared spectroscopy was obtained for the flavones. Four flavones were tested for their schistosomicidal in vitro activity and showed great potential as antiparasitics. In addition, these flavones were tested for their enzymatic activity against the ATP-diphosphohydrolase enzyme, which four of them showed an interesting potential against the inhibition of this enzyme.

The flavone 3,5,7-trihydroxy-6-methoxyflavone was isolated from leaf extracts of Chromolaena leivensis (Hieron), commonly named plant of cancer. It was identified based on their physicochemical propierties and spectroscopic data. This compound presented a methoxylation at C6, this is uncommon in flavonoids and which may confer some specificity of its biological activity. The cytotoxic activity of this flavonoid was determined on PC3 (prostate), MDA- MB-231 (breast), HT29 (colon), SiHa (cervix) and A549 (lung) cancer cells, using MTT assay, to assess if the flavonoid contributes to the anticancer activity previously proposed for Chromolaena leivensis. The cytotoxic activity of the 3,5,7-trihydroxy-6- methoxy flavone was similar to that obtained for the flavonoid quercetin but was low compared with the positive control vincristine sulphate. The better value of the inhibitory concentration of fifty percent (IC50) 150 μ M, was achieved on SiHa cell line, while the lower activity: 4008 μ M, was obtained on HT29 cancer cell line. However, severe morphological changes were detected on cytoskeleton and nucleus of the SiHa cells detected by immunofluorescence microscopy analysis of cells exposed to the half of the IC50 concentration obtained for the flavonoid. Data indicate that the flavonoid contributes to the anticancer activity of the extracts of leaves from Chromolaena leivensis, and could broadening the spectrum of flavonoids activity against various types of cancer non hormone-dependent.

Le travail de recherche présenté dans ce mémoire de thèse a été centré sur une nouvelle famille de flavones aux propriétés antivirales. Mon travail de thèse avait pour premier objectif d'améliorer la synthèse de la ladanéine (tête de série) et permettre l'accès à d’autres analogues. Un développement méthodologique a permis de mettre au point une synthèse compatible avec les procédés industriels qui permette d'améliorer les rendements et de raccourcir significativement les délais d'obtention. De plus, aucune purification par colonne de silice n’est nécessaire. Une étude physico-chimique détaillée a ensuite été menée. Les propriétés acido-basiques de la série de composés ont d'abord été évaluées avant l'étude des propriétés électrochimiques. Ces données sont déterminantes pour une meilleure compréhension du mécanisme d'action de ces flavones. La complexation au Fe(III) a été également démontrée comme essentielle pour l’activité antivirale de ces composés. Les propriétés de complexation de ce cation ont donc été étudiées et ont apporté des informations importantes. Finalement, dans le but d’améliorer les propriétés pharmacocinétiques de ces agents virucides, des formulations originales avec le Mg(II), cation biocompatible, ont été élaborées et étudiées. / The research work presented in this manuscript was centered on a novel flavone series displaying potent antiviral activities toward enveloped viruses such as HCV. The first goal of my research work was to improve the synthesis of ladanein (the lead antiviral compound) and to allow an easy access to a broad range of analogues. A methodological approach allowed setting up a synthetic route compatible with industrial processes with high yields and significantly shortened preparation time. Furthermore, no silica gel column chromatography was needed throughout the synthetic route. A thorough physico-chemical study was then undertaken. The acido-basic properties of this homogenous series of compounds were first evaluated prior to the investigation of their electrochemical parameters. These data are essential for a deeper understanding of the mechanism of action of these polyphenolic compounds. Fe(III) was shown to be essential for the antiviral activity of these compounds and, hence, the Fe(III) complexation properties of the flavones have been studied and provided important information. Last but not least, in order to improve the pharmacokinetic properties of the flavones, original formulation approaches using the biocompatible Mg(II) cation were undertaken and thoroughly investigated.

Made available in DSpace on 2015-05-14T12:59:26Z (GMT). No. of bitstreams: 1 parte1.pdf: 6006358 bytes, checksum: a086233e056cff34f3845a08fc1c96a8 (MD5) Previous issue date: 2011-09-01 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The family Asteraceae is the largest angiosperm family and represents nearly 10% of the world's total flora. The family has been one of the most studied, in large part due to the promising chemical compounds produced by this group. Aiming at contributing to the chemotaxonomic study of the family Asteraceae , Praxelis clematidea e Verbesina macrophylla were submitted to a phytochemical study to isolate its chemical constituents, through usual chromatographic methods, and after identifying them by means of spectroscopic methods such as 1H and 13C NMR, with the add of two-dimensional techniques, besides comparison with literature data. Chemical study of the aerial parts of V. macrophylla resulted in the isolation of six compounds (p-coumaric acid, 6-E-p-cumaroil-4α-hydroxieudesmane, 6-Z-p-cumaroil- 4α-hydroxieudesmane, bornil-p-cis-cumarate, bornil-p-trans- coumarate and phydroxybenzoic acid). One flavone (5,7,3 ',4'-tetrahydroxyflavone) was isolated from ethyl acetate extract of the aerial parts of P. clematidea and six flavones were isolated from chloroform extract (4 ,5,7- trihydroxyflavone; 4 ,5-dihydroxy-7 methoxyflavone; 5-hydroxy-4´,7 dimethoxyflavone; 4 ,5,7- trimethoxyflavone; 5,4 - dihydroxy-6,7 dimethoxyflavone and 4 ,5,6,7- tetramethoxyflavone), all flavonoids are described by first time in the specie. The flavones of chloroform extract of P. clematidea were tested for their toxicity against Staphylococcus aureus SA-1199B, a strain possessing the NorA efflux pump. The flavones tested did not show any significant antibacterial activity against the Staphylococcus aureus strain used, but were able to modulate bacterial drug resistance. This property might be related to the degree of lipophilicity of the flavones conferred by the methoxyl groups, since 4 ,5,6,7 tetramethoxyflavone the most methoxylated compound, reduced the minimal inhibitory concentration of the drug (Norfloxacin)16-fold. / A família Asteraceae é a maior família de angiospermas e representa quase 10% da flora mundial. A família tem sido uma dos mais estudadas, em grande parte devido aos compostos químicos promissores produzido por este grupo. Visando contribuir para o estudo quimiotaxonômicos da família Asteraceae, Praxelis clematidea e Verbesina macrophylla foram submetidos a um estudo fitoquímico para isolar seus constituintes químicos, através de métodos cromatográficos usuais, e depois para identificá-los por meio de métodos espectroscópicos, tais como RMN de 1H e 13C uni e bidimensionais, além de comparação com dados da literatura. O estudo químico das partes aéreas de V. macrophylla resultou no isolamento de seis compostos (ácido p-cumárico, 6-E-p-cumaroil-4α-hidroxieudesmano, 6-Z-p-cumaroil- 4α-hidroxieudesmano, bornil-p-cis-cumarato, bornil-p-trans-cumarato e ácido phidroxibenzóico). Uma flavona (5,7,3',4'-tetrahidroxiflavona) foi isolado do extrato acetato de etila das partes aéreas de P. clematidea e seis flavonas foram isolados a partir de extrato clorofórmico (4 ,5,7- trihidroxiflavona ; 4 ,5-dihidroxi-7 metoxiflavona; 5-hidroxi-4´,7-dimetoxiflavona; 4 ,5,7-trimetoxiflavona; 5,4 -dihidroxi-6,7 dimetoxiflavona e 4 ,5,6,7- tetrametoxiflavona), todos os flavonóides estão sendo descritos pela primeira vez na espécie. O flavonas do extrato clorofórmico de P. clematidea foram testadas para a toxicidade contra Staphylococcus aureus SA- 1199B, uma cepa que possuem a bomba de efluxo NorA. O flavonas testadas não mostraram qualquer atividade antibacteriana significativa contra a cepa Staphylococcus aureus usados, mas foram capazes de modular a resistência bacteriana à drogas. Esta propriedade pode estar relacionado com o grau de lipofilicidade do flavonas conferidos pelos grupos metoxila, já que a 4, 5,6,7 tetramethoxyflavone o composto mais metoxilados, reduziu a concentração inibitória mínima do fármaco (Norfloxacina) 16 vezes.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-23T14:40:10Z No. of bitstreams: 1 luisamariasilveiradealmeida.pdf: 3706782 bytes, checksum: 1b4e01bcd663e5b0167c387beb0d0e2d (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:31:05Z (GMT) No. of bitstreams: 1 luisamariasilveiradealmeida.pdf: 3706782 bytes, checksum: 1b4e01bcd663e5b0167c387beb0d0e2d (MD5) / Made available in DSpace on 2016-09-26T20:31:05Z (GMT). No. of bitstreams: 1 luisamariasilveiradealmeida.pdf: 3706782 bytes, checksum: 1b4e01bcd663e5b0167c387beb0d0e2d (MD5) Previous issue date: 2015-07-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A esquistossomose é uma doença que afeta cerca de 200 milhões de pessoas no mundo e mais de 600 milhões estão expostas ao risco de contraí-la, sendo que no Brasil, o Estado de Minas Gerais é um dos mais afetados com esta parasitose. Atualmente, o único fármaco disponível para o tratamento desta doença é o praziquantel (PZQ). No entanto, este medicamento já está no mercado há décadas e tem demonstrado relatos de ineficácia. Neste contexto, extratos e metabólitos secundários obtidos de espécie do gênero Artemisia (Asteraceae) têm demonstrado expressiva atividade esquistossomicida. Assim, o presente trabalho descreve o estudo fitoquímico do extrato diclorometânico das folhas de Artemisia absinthium L. (AAF), bem como a avaliação da atividade esquistossomicida in vitro dos extratos AAF e das raízes, do óleo essencial e do metabólito obtido. O estudo fitoquímico, do AAF, culminou no isolamento e identificação de dois metabólitos: uma flavona, artemetina e uma lactona sesquiterpênica, hidroxipelenolídeo. No estudo esquistossomicida in vitro foi utilizado vermes adultos de S. mansoni da linhagem BH e os parâmetros avaliados foram mortalidade, motilidade e alterações tegumentares. Os resultados deste estudo demonstraram que o extrato diclorometânico bruto (AAF), na concentração de 200 μg/mL, possui expressiva atividade esquistossomicida in vitro ao ser capaz de causar a morte de 100% dos parasitos após 24 h de incubação. Em relação à atividade esquistossomicida do extrato bruto da raiz (200 μg/mL), este foi capaz de provocar a morte de todos os vermes após 48 h. O óleo essencial da A. absinthium L. (100 µg/mL) apresentou atividade esquistossomicida moderada sendo capaz de causar 60% de mortalidade nos parasitos após 48 h de incubação. Dentre as substâncias isoladas, a artemetina, foi submetida ao ensaio de atividade esquistossomicida e não foi ativa. Estudos adicionais de avaliação esquistossomicida devem ser realizados com o extrato bruto e metabólitos de A. absinthium L. com o intuito de se identificar as moléculas responsáveis pela atividade esquistossomicida in vitro observada pelo extrato AAF. / Schistosomiasis is a disease that affects more than 200 million individuals in the world and 600 million people remain under risk of infection. In Brazil, the Minas Gerais state is one of the most affected by this disease. Nowadays, the only drug available for schistosomiasis treatment is praziquantel (PZQ). However, this drug is already on market for decades and has shown ineffectiveness. In this context, extract and secondary metabolites of the genus Artemisia (Asteraceae) have shown an expressive schistosomicidal activity. Thus, the present work describes the phytochemical study of the dichloromethane extract of Artemisia absinthium L. leaves (AAF), as well as in vitro schistosomicidal evaluation of AAF, crude roots extracts, essential oil and metabolite. The phytochemical study of AAF allowed the isolation and identification of two metabolites: one flavone, artemetin and one sesquiterpene lactone, hydroxypelenolide. In the in vitro schistosomicidal study, was used adult worms of the S. mansoni BH strain and the parameters evaluated were mortality, motility and alterations tegumental surface. The results showed that AAF, at 200 μg/mL, presents expressive schistosomicidal activity being able to cause 100% of death in parasites after 24 h of incubation. Regarding the schistosomicidal activity of the extract crude roots extract (200 μg/mL), was able to kill all the parasites after 48 h. The A. absinthium L. essential oil (100 mg / mL) showed moderate schistosomicidal activity being able to cause 60% mortality of parasites after 48 h of incubation. Among the isolated compounds, artemetin, was subjected to the schistosomicidal activity test and was inactive. Additional schistosomicidal assays should be carried out with A. absinthium L. crude extract and metabolites in order to identify the molecules responsible for schistosomicidal in vitro activity observed by AAF.

The development of drugs and therapeutic agents for combating infections and human malignancies continues to be a forefront area in both academic and industrial research. This is driven by the rapid emergence of multi-drug resistant bacterial strains and accumulating mutations in cancer targets that is quickly rendering our current arsenal of drugs ineffective for these therapies. Unless new drugs with novel mechanisms of action are identified and developed at a faster pace, we face a losing battle in managing these diseases. The first part of this work concerns with the natural product Simocyclinone D8 (SD8). Simocyclinone D8 is an angucyclinone antibiotic that inhibits DNA gyrase with a novel mechanism of action that has been termed competitive inhibition. Simocyclinone D8 was found to inhibit the growth of both Gram-(+ve) and Gram-(–ve) organisms and also inhibit a fluoroquinolone resistant mutant of DNA gyrase. Inspired by the structure and novel mechanism of action that SD8 displays, we synthesized analogues based on the co-crystal structure of SD8 with DNA gyrase. These compounds were found to inhibit DNA gyrase, albeit by a different mechanism of action than that of SD8. We also conducted studies towards the total chemical synthesis of SD8 and made three out of the four fragments in SD8 in decent yields. The second part of this work is focused on the development of a substrate-competitive covalent inhibitor for protein kinase B (AKT). AKT is a valid target for cancer research with two compounds currently in late stage clinical trials. Developing substrate- competitive inhibitors for kinases is a novel approach in targeting them, with very few examples in the literature. This mechanism has been postulated to overcome common resistance mutations that cancer targets harbor. A major drawback in this approach is the low binding affinity for peptide substrates by kinases. We circumvented this problem of affinity by utilizing a covalent mode of binding and synthesized a potent non-peptide active-site directed irreversible compound that inhibits AKT. Further studies on this compound are underway and are expected to yield a compound that can be used as a therapeutic agent or as a probe for AKT.

Submitted by Cristhiane Guerra (cristhiane.guerra@gmail.com) on 2017-02-03T15:51:13Z No. of bitstreams: 1 arquivototal.pdf: 2439266 bytes, checksum: 852d348e101a0679a14c24845b557b1e (MD5) / Made available in DSpace on 2017-02-03T15:51:13Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2439266 bytes, checksum: 852d348e101a0679a14c24845b557b1e (MD5) Previous issue date: 2015-07-31 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Phenolic compounds, among them the flavonoids, are holders of antimicrobial, antioxidant and anti-inflammatory effects, but not free from toxicity and/or adverse effects, that's why research in this area, whether they are in silico, in vitro and/or in vivo approach have been intensified to ensure the safe use of these molecules. Thus, the aim of this study was to investigate the probable pharmacological activities, toxicity and antibacterial and antioxidant effects of flavonoid flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone, tracing a structure-activity relationship of such substances. It was investigated the pharmacological, pharmacokinetics and theoretical toxicological characteristics of flavonoids using in silico testing with the PASS online and Osiris softwares; the cytotoxicity on human erythrocytes of blood types A, B and O positive and negative Rh factor, running the models of hemolysis and Erythrocyte Osmotic Fragility (EOF); was analysed the antimicrobial activity in front of Gram-positive (B. subtilis CCT 0516, S. aureus ATCC 25619 and S. aureus ATCC 25925) and Gram-negative, including clinical importance (P. aeruginosa ATCC 8027, P. aeruginosa ATCC 23243, E. coli ATCC 2536, E. coli 101, E. coli 103, E. coli 104, E. coli 105 and E. coli 108); assessed the oxidant and antioxidant potential of these molecules in the presence of Reactive Oxygen Species (ROS - H2O2) and phenylhydrazinium (Ph) and, finally, the genotoxicity using the micronucleus test. The results obtained revealed numerous probable pharmacological activities to the flavonoids, as integrity agonists and membrane permeability inhibitors, anaphylatoxin receptor antagonists, inhibitors of kinase and peroxidase, antimutagenic potential and vase-protecting capacity; do not present significant theoretical toxicity risks and have good oral bioavailability. The 4 flavonoids have shown moderate hemolysis at concentrations of 500 and 1000 μg/mL, the example of 3-hydroxyflavone which induced 20.2 % and 53 % of hemolysis, respectively, in blood type A, Rh+; the flavonoids hydroxylated protected cells types A and O from osmotic stress. All flavonoids exhibited moderate antibacterial activity against Gram-positive strains and Gram-negative, being the flavone bactericide in the concentration of 200 μg/mL to the strains of P. aeruginosa ATCC 8027, S. aureus ATCC 25619 and E. coli 104, while other flavonoids have bacteriostatic action. It did not promote oxidation of erythrocyte and behaved as scavengers and antioxidants of H2O2 and phenylhydrazinium and finally the flavone did not show genotoxicity compared to cyclophosphamide, a proven genotoxic agent. It is concluded that the flavone, 3-hydroxyflavone, 5-hydroxyflavone and 6- hydroxyflavone have different pharmacological activities, good bioavailability and low theoreticals toxicity, reduced cytotoxicity, absence of genotoxicity as well as being moderate antibacterial and antioxidant, showing, with this study, the importance of the inclusion of computational chemistry techniques for targeting evaluation protocols of the biological effects of the molecules. / Compostos fenólicos, dentre eles os flavonoides, são detentores de efeitos antimicrobiano, antioxidante e anti-inflamatório, porém não isentos de toxicidade e/ou efeitos adversos, por isso pesquisas nesta área, sejam elas com uma abordagem in silico, in vitro e/ou in vivo têm se intensificado para que se garanta a segurança no uso dessas moléculas. Assim, o presente estudo se propôs a investigar as prováveis atividades farmacológicas, a toxicidade e os efeitos antibacteriano e antioxidante do flavonoide flavona e de seus derivados hidroxilados: 3-hidroxiflavona, 5-hidroxiflavona e 6-hidroxiflavona, traçando uma relação estrutura-atividade das referidas substâncias. Para tanto, investigou-se as características farmacológica, farmacocinética e toxicológica teóricas dos flavonoides utilizando ensaios in silico com os softwares PASS online e Osíris; a citotoxicidade sobre eritrócitos humanos dos tipos sanguíneos A, B e O e fator Rh positivo e negativo, executando-se os modelos de hemólise e Fragilidade Osmótica Eritrocitária (FOE); analisou-se a atividade antimicrobiana frente a bactérias Gram-positivas (B. subtilis CCT 0516, S. aureus ATCC 25619 e S. aureus ATCC 25925) Gram-negativas, inclusive de importância clínica (P. aeruginosa ATCC 8027, P. aeruginosa ATCC 23243, E. coli ATCC 2536, E. coli 101, E. coli 103, E. coli 104, E. coli 105 e E. coli 108); avaliou-se o potencial oxidante e antioxidante das referidas moléculas na presença de Espécies Reativas de Oxigênio (EROs - H2O2) e da fenilhidrazina (Ph) e, por último, a genotoxicidade por meio do teste do micronúcleo. Os resultados obtidos revelaram numerosas prováveis atividades farmacológicas para os flavonoides, como agonistas da integridade e inibidores da permeabilidade membranar, antagonistas do receptor de anafilatoxina, inibidores de quinase e peroxidase, potencial antimutagênico e capacidade vasoprotetora; não apresentam significativos riscos teóricos de toxicidade e detêm uma boa biodisponibilidade oral. Os 4 flavonoides demonstraram moderada hemólise nas concentrações de 500 e 1000 μg/mL, a exemplo da 3-hidroxiflavona que induziu 20,2 e 53 % de hemólise, respectivamente, no sangue tipo B,Rh-; os flavonoides hidroxilados protegeram os eritrócitos tipos A e O do estresse osmótico. Todos os flavonoides exibiram moderada atividade antibacteriana contra cepas Gram-positivas e Gram-negativas, sendo a flavona bactericida na concentração de 200 μg/mL para as linhagens de P. aeruginosa ATCC 8027, S. aureus ATCC 25619 e E. coli 104, enquanto que os demais flavonoides têm ação bacteriostática. As substâncias não promoveram oxidação dos eritrócitos e comportaram-se como sequestradores e antioxidantes de H2O2 e fenilhidrazina e, por fim, a flavona não apresentou genotoxicidade quando comparado com a ciclofosfamida, um comprovado agente genotóxico. Conclui-se que flavona, 3-hidroxiflavona, 5-hidroxiflavona e 6-hidroxiflavona possuem variadas atividades farmacológicas, boa biodisponibilidade e baixa toxicidade teóricas, reduzida citotoxicidade, ausência de genotoxicidade, além de serem moderadamente antibacterianos e antioxidantes, evidenciando-se, com este estudo, a importância da inserção de técnicas de química computacional para o direcionamento de protocolos de avaliação de efeitos biológicos de moléculas.