The n-butanol extract of aerial parts of Cordyline australis demonstrated antifungal activity. n-Butanol and chloroform extracts of dried or fresh leaves of C. australis afforded a steroidal glycoside, which was identified as 5α-spirost-25(27)-en-3β-ol 3-O{O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside}, saponin 1. This spirostanol glycoside showed strong antifungal activity towards Trichophyton mentagrophytes and some aspecific activity and cytotoxicity against MRC5 cell. The chloroform extract of fresh leaves of C. australis yielded a second new spirostanol glycoside which was identified as 5α-spirost-25(27)-ene-1β,3β-diol 1-{O-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranoside}, saponin 2. The n-butanol extracts of senescent leaves of C. australis afforded a third new spirostanol glycoside that was identified as 5α-spirost-25(27)-ene-1β,3β-diol 1-{O-β-D- fucopyranoside, saponin 3. A mixture of two isomeric flavonoid glycosides was isolated from dried leaves of C. australis and shown to be a ca 1:1 mixture of isorhamnetin-3-O-{O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside}, 4 and isorhamnetin-3-O-{O-α-L-rhamnopyranosyl-(1→6)-β-D-galactopyranoside}, 5. Three other known steroidal glycosides, β-sitosterol glucoside, 6, prosapogenin A of dioscin, 7, and trillin, 8 were also isolated from the leaves of C. australis. The n-butanol extract of dried stems of C. australis afforded (25S)-5α-spirostane-1β,3α-diol 1-{O-β-D-glucopyranoside}, 9. This spirostanol glycoside showed moderate cytotoxicity against Herpes simplex type I virus (ATCC VR733) and Polio Virus Type I (Pfiser vaccine strain).

Yes / There are many human oral antimicrobial peptides responsible for playing important roles including maintenance, repairing of oral tissues (hard or soft) and defense against oral microbes. In this review we have highlighted the biochemistry, physiology and proteomics of human oral histatin peptides, secreted from parotid and submandibular salivary glands in human. The significance of these peptides includes capability for ionic binding that can kill fungal Candida albicans. They have histidine rich amino acid sequences (7–12 family members; corresponding to residues 12–24, 13–24, 12–25, 13–25, 5–11, and 5–12, respectively) for Histatin-3. However, Histatin-3 can be synthesized proteolytically from histatin 5 or 6. Due to their fungicidal response and high biocompatibility (little or no toxicity), these peptides can be considered as therapeutic agents with most probable applications for example, artificial saliva for denture wearers and salivary gland dysfunction conditions. The objectives of current article are to explore the human histatin peptides for its types, chemical and biological aspects. In addition, the potential for therapeutic bio-dental applications has been elaborated. / King Saud University

Orientador: José Benedito Oliveira Amorim / Coorientadora: Liliana Scorzoni / Banca: Mônica Fernandes Gomes / Banca : Dayane Batista Tada / Resumo: A epidemiologia das infecções causadas por Candida sofreu mudanças nos últimos anos. Embora Candida albicans ainda seja o principal patógeno causador de candidíase, relatos recentes reportam o aumento da incidência de infecções causadas por espécies de Candida não-albicans. A toxicidade dos fármacos antifúngicos utilizados juntamente com o desenvolvimento da resistência tem se tornado um sério problema clínico. Com isso, atualmente existe a urgência na descoberta de novos compostos com atividades antifúngicas. Objetivos: avaliar a atividade antifúngica do fármaco Cloridrato de Verapamil, determinar a Concentração Inibitória Mínima (CIM) e a Concentração Fungicida Mínima (CFM), frente à Candida albicans ATCC 18804, Candida krusei ATCC 6258, Candida parapsilosis ATCC 90018 e Candida glabrata ATCC 9030. Além de avaliar a citotoxicidade do fármaco em queratinócitos humanos (HaCaT). Metodologia: a determinação da CIM foi realizada pela técnica de microdiluição de acordo com The European Committee on Antimicrobial Susceptibility Testing (EUCAST). A CFM foi determinada por plaqueamento em ágar Sabouraud de alíquotas provenientes das diluições do ensaio de microdiluição. A avaliação da citotoxicidade foi realizada pela técnica de redução da resazurina, sendo possível avaliar a atividade mitocondrial das células HaCaT. Resultados: o fármaco Cloridrato de Verapamil demonstrou atividade antifúngica contra as quatro espécies patogênicas de Candida, com o valor de CIM de 1250 µM; ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The epidemiology of Candida infections has changed in recent years. Although Candida albicans is still the main pathogen causing candidiasis, recent reports have reported an increase in the incidence of infections caused by nonalbicans Candida species. The toxicity of the antifungal drugs used together with the development of resistance has become a serious clinical problem. With this, there is now an urgency in the discovery of new compounds with antifungal activities. Objectives: To evaluate the antifungal activity of the drug Verapamil Hydrochloride, to determine the Minimum Inhibitory Concentration (MIC) and the Minimum Fungicidal Concentration (CFM) against Candida albicans ATCC 18804, Candida krusei ATCC 6258, Candida parapsilosis ATCC 90018 and Candida glabrata ATCC 9030 In addition to evaluating the cytotoxicity of the drug in human keratinocytes (HaCaT). Methodology: MIC determination was performed by the microdilution technique according to The European Committee on Antimicrobial Susceptibility Testing (EUCAST). The CFM was determined by plating on Sabouraud agar from aliquots from the dilutions of the microdilution assay. The evaluation of cytotoxicity was performed using the resazurin reduction technique, and it was possible to evaluate the mitochondrial activity of HaCaT cells. Results: The drug Verapamil Hydrochloride demonstrated antifungal activity against the four pathogenic species of Candida, with MIC value of 1250 μM; CFM value greater than 1250 ... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:29:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-10-30Bitstream added on 2014-06-13T19:58:54Z : No. of bitstreams: 1 assonuma_mm_me_araiq.pdf: 1464819 bytes, checksum: 17eb2d0c6ea3f6e36f0e6b0b5c32a2fb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / É notável a crescente demanda comercial pelos extratos das folhas de “Chá de Bugre” (Cordia ecalyculata Vell.) principalmente para a sua aplicação como supressor de apetite e agente cicatrizante. Trata-se de uma planta de origem sul americana sendo no Brasil muito comum nos estados de Minas Gerais, Bahia, Goiás, Paraná e Santa Catarina. É uma planta da família boraginaceae utilizada na fitoterapia brasileira como diurético, febrífugo, estimulante circulatório e também como inibidora do apetite, embora poucos relatos científicos comprovem tais atividades. Uma ampla revisão bibliográfica foi realizada e até o momento verificou- se que são poucos os estudos referentes aos constituíntes químicos presentes na espécie, destacando-se alcalóides como a cafeína, a alantoína e ácido alantóico; glicosídeos como a consolidina; taninos e pigmentos, além de compostos inorgânicos como o potássio. Órgãos regulatórios nacionais e internacionais responsáveis pela avaliação dos parâmetros de qualidade dos extratos comercializados tem sido cada vez mais incisivos quanto à padronização focando em marcadores específicos, metodologiasanalíticas validadas para a determinação de tais marcadores, estudos de estabilidade e também comprovações científicas que atestem as atividades biológicas esperadas. De acordo com os objetivos propostos, realizou-se inicialmente uma ampla revisão bibliográfica focando aspectos botânicos, químicos e farmacológicos da espécie. Posteriormente, realizou-se o desenvolvimento e também a validação de uma metodologia analítica cromatográfica capaz de determinar a alantoína nas folhas e também nos extratos obtidos de chá de bugre. Por fim, foi realizada a avaliação farmacológica da espécie, focando em ensaios do tipo antihemorrágico antifúngico, antioxidante e citotóxico para células normais e tumorais... / The increasing demand for commercial extracts of Chá de Bugre” (Cordia ecalyculata Vell.) is remarkable, especially for its use as appetite suppressant and wound healing agent. The specie is a plant originated from South America and widely spread in Brazil, in the states of Minas Gerais, Bahia, Goiás, Parana and Santa Catarina. It is a plant of the family boraginaceae, used in the Brazilian phytotherapy as diuretic, antipyretic, circulatory stimulant and appetite suppressant, but few scientific reports corroborate such activities. An extensive literature review has been carried out and so far it appears that there are few studies regarding the chemical constituents present in this species like alkaloids such as caffeine, allantoin and allantoic acid, glycosides as consolidine, in addition to tannins, pigments, and inorganic compounds such as potassium. National and international regulatory departments responsible for assessment of parameters related to the quality of the extracts have been increasingly incisive focusing on the standardization of specific markers, validation of analytical methods for the determination of such markers, stability studies and also scientific evidence that demonstrates the expected biological activities. According to the proposed objectives, a deep literature review has been initially carried out focusing on botanical, chemical and pharmacological aspects of C. ecalyculata. Subsequently, a chromatographic analytical methodology capable of determining allantoin in the leaves and also in extracts of “chá de bugre” has been developed and validated. Finally, we performed a pharmacological evaluation of the species, focusing on the antihemorrhagic, antifungal, antioxidant and cytotoxic activities to both normal and tumor cells. Biological assays evidenced that the ethyl acetate phase of aqueous ethanol extract of leaves showed hemorrhage inhibition ... (Complete abstract click electronic access below)

Orientador: Dulce Helena Siqueira Silva / Banca: Clélia Akiko Hiruma-Lima / Banca: Carmen Lucia Cardoso / Resumo: É notável a crescente demanda comercial pelos extratos das folhas de "Chá de Bugre" (Cordia ecalyculata Vell.) principalmente para a sua aplicação como supressor de apetite e agente cicatrizante. Trata-se de uma planta de origem sul americana sendo no Brasil muito comum nos estados de Minas Gerais, Bahia, Goiás, Paraná e Santa Catarina. É uma planta da família boraginaceae utilizada na fitoterapia brasileira como diurético, febrífugo, estimulante circulatório e também como inibidora do apetite, embora poucos relatos científicos comprovem tais atividades. Uma ampla revisão bibliográfica foi realizada e até o momento verificou- se que são poucos os estudos referentes aos constituíntes químicos presentes na espécie, destacando-se alcalóides como a cafeína, a alantoína e ácido alantóico; glicosídeos como a consolidina; taninos e pigmentos, além de compostos inorgânicos como o potássio. Órgãos regulatórios nacionais e internacionais responsáveis pela avaliação dos parâmetros de qualidade dos extratos comercializados tem sido cada vez mais incisivos quanto à padronização focando em marcadores específicos, metodologiasanalíticas validadas para a determinação de tais marcadores, estudos de estabilidade e também comprovações científicas que atestem as atividades biológicas esperadas. De acordo com os objetivos propostos, realizou-se inicialmente uma ampla revisão bibliográfica focando aspectos botânicos, químicos e farmacológicos da espécie. Posteriormente, realizou-se o desenvolvimento e também a validação de uma metodologia analítica cromatográfica capaz de determinar a alantoína nas folhas e também nos extratos obtidos de chá de bugre. Por fim, foi realizada a avaliação farmacológica da espécie, focando em ensaios do tipo antihemorrágico antifúngico, antioxidante e citotóxico para células normais e tumorais ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The increasing demand for commercial extracts of "Chá de Bugre" (Cordia ecalyculata Vell.) is remarkable, especially for its use as appetite suppressant and wound healing agent. The specie is a plant originated from South America and widely spread in Brazil, in the states of Minas Gerais, Bahia, Goiás, Parana and Santa Catarina. It is a plant of the family boraginaceae, used in the Brazilian phytotherapy as diuretic, antipyretic, circulatory stimulant and appetite suppressant, but few scientific reports corroborate such activities. An extensive literature review has been carried out and so far it appears that there are few studies regarding the chemical constituents present in this species like alkaloids such as caffeine, allantoin and allantoic acid, glycosides as consolidine, in addition to tannins, pigments, and inorganic compounds such as potassium. National and international regulatory departments responsible for assessment of parameters related to the quality of the extracts have been increasingly incisive focusing on the standardization of specific markers, validation of analytical methods for the determination of such markers, stability studies and also scientific evidence that demonstrates the expected biological activities. According to the proposed objectives, a deep literature review has been initially carried out focusing on botanical, chemical and pharmacological aspects of C. ecalyculata. Subsequently, a chromatographic analytical methodology capable of determining allantoin in the leaves and also in extracts of "chá de bugre" has been developed and validated. Finally, we performed a pharmacological evaluation of the species, focusing on the antihemorrhagic, antifungal, antioxidant and cytotoxic activities to both normal and tumor cells. Biological assays evidenced that the ethyl acetate phase of aqueous ethanol extract of leaves showed hemorrhage inhibition ... (Complete abstract click electronic access below) / Mestre

A incidÃncia de infecÃÃes oportunistas causadas por fungos, com destaque para as leveduras do gÃnero Candida vem aumentando substancialmente. Estudos relatam que tem sido observado um notÃvel crescimento de infecÃÃes por espÃcies nÃo albicans (Candida tropicalis, Candida glabrata, Candida parapsilosis e Candida krusei). Isolados clÃnicos resistentes aos azÃlicos, em especial ao fluconazol, sÃo cada vez mais relatados. As naftoquinonas sÃo uma importante classe de molÃculas biologicamente ativas, apresentando atividades antibacteriana, antifÃngica, antiviral, anti-inflamatÃria, antipirÃtica, anticancerÃgena e tripanocida e tem sido amplamente testadas em vÃrios estudos farmacolÃgicos. Nos Ãltimos anos intensificou-se o interesse nestas substÃncias, nÃo sà devido à sua importÃncia em processos bioquÃmicos vitais, como tambÃm ao destaque cada vez maior que apresentam em variados estudos farmacolÃgicos. O presente trabalho buscou avaliar e comparar o efeito antifÃngico de naftoquinonas frente a cepas de Candida tropicalis resistentes e sensÃveis ao fluconazol, utilizando diferentes tÃcnicas tais como mÃtodos de microdiluiÃÃo em caldo, procedimentos de citometria de fluxo e ensaio do Cometa. Utilizamos sete cepas de Candida tropicalis resistentes ao fluconazol para esse estudo, as quais foram isoladas de sangue e faziam parte da colecÃÃo de leveduras do LaboratÃrio de BioprospecÃÃo Experimental em leveduras (LABEL), afiliado com a Faculdade de FarmÃcia da Universidade Federal do Cearà . Foi utilizado trÃs compostos de naftoquinonas frente à 07 cepas de Candida tropicalis e foram submetidas aos testes de Sensibilidade in vitro , onde apresentaram uma potente atividade antifÃngica. AtravÃs da Citometria de Fluxo, foi possÃvel avaliar alteraÃÃes morfolÃgicas e de integridade da membrana significativas desses compostos frentes Ãs cepas, alÃm de disfunÃÃo mitocondrial e produÃÃo de espÃcies reativas de oxigÃnio. AtravÃs do ensaio do Cometa foi possÃvel encontrar danos significativos ao DNA. Em sÃntese, os resultados sugerem que estes compostos podem ser usados como agentes antifÃngicos para o tratamento de candidemias / The incidence of opportunistic infections caused by fungi, with emphasis on Candida species has increased substantially. Studies report that there has been a notable increase of infections by non-albicans species (Candida tropicalis, Candida glabrata, Candida parapsilosis and Candida krusei). Clinical isolates resistant to azoles, particularly fluconazole, are increasingly reported. The naphthoquinones are an important class of active molecules biologically presenting antibacterial, antifungal, antiviral, antiinflammatory, antipyretic, anti-cancer and trypanocidal and has been tested extensively in several pharmacological studies. In recent years intensified the interest in in this substances, not only due to your importance in vital biochemical processes as well as the increasing emphasis that they show in various pharmacological studies. This study aimed to evaluate and compare the effect of antifungal naphthoquinones against strains of Candida tropicalis resistant and susceptible to fluconazole, using different techniques such as broth microdilution methods, procedures Flow Cytometry procedures and Comet assay. We use seven strains of Candida tropicalis resistant to fluconazole for this study, which were isolated from blood and were part of the collection of yeasts Experimental Laboratory Bioprospecting in yeast (LABEL), affiliated with the Faculty of Pharmacy, Federal University of CearÃ. We used three compounds of naphthoquinones against the seven strains of Candida tropicalis and were subjected to in vitro sensitivity tests, which showed an antifungal activity potent. Through Flow Cytometry, it was possible to assess morphological changes and membrane integrity of these compounds fronts to significant strains in addition to mitochondrial dysfunction and production of reactive oxygen species. Through the Comet assay was possible to find significant damage to DNA. In summary, the results suggest that these compounds may be used as antifungal agents for the treatment of candidemia

Strain MS14, exhibiting antifungal activity, was classified to belong to Burkholderia contaminans. Occidiofungin produced by strain MS14 is an octapeptide dedicated to a broad range of antifungal activities of the bacterium. The 58.2-kb genomic fragment containing 18 open reading frames (ORFs), named occidiofungin (occ) gene cluster, is required for occidiofungin production. Putative proteins encoded by five nonribosomal peptide synthetase genes (occA – occE) of the gene cluster were predicted to contain the catalytic modules responsible for the biosynthesis of occidiofungin. Transcription of all the ORFs identified in the region except ORF1 and ORF16 was regulated by both ambR1 and ambR2, the LuxR-type regulatory genes located at the left border of the cluster. The functional ambR1 gene was essential for transcription of ambR2, and constitutive expression of ambR2 did not restore the phenotype of the mutant MS14GG44(ambR1::nptII). Sequence analysis revealed that the occ gene cluster shared high similarity (99% nucleotide coverage and 91% identity) to an uncharacterized DNA region of B. ambifaria strain AMMD. The gene cluster was not found in other Burkholderia strains available in GenBank (nucleotide coverage < 24%). Analysis of G+C composition and prediction using “IslandPick” indicate that the occ gene cluster has possibly been horizontally transferred between bacteria. In addition, the absence of the gene cluster in clinical strains of Burkholderia indicates that occidiofungin is not required for potential human pathogenesis. The findings have provided insights into the development of antifungal medicines and agricultural fungicides based on occidiofungin.

Microbe resistence is a serious issue, especially as they have become resistant to most well known drugs. Therefore this is considered as a global problem and is now dealt with at a poitical level. Since no new classes of antimicrobial agents have been discovered in the past three deacdes, the development of new drugs is extremely urgent. Therefore the aim of this project was to synthesise derivatives of benzimidazole, and then assesses their antimicrobial activities in vitro by using disc (well) diffusion and MICs tests. A total of 69 benzimidazole derivatives, with substituents at positions 1, 2, and 5, were synthesised, characterised and tested against selected bacteria and fungi. In addition, six bezimidazole silver complexes were prepared and evaluated for their antimicrobial behavior. The SAR showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. Some promising results were obtained. In particular, 5 compounds displayed antibacterial activity against two MRSA strains with MIC values corresponding to ciprofloxacin, which can be considered significant. The compounds have some common features; four possess 5-chloro or 5-bromo substituents; two are derivatives of (S)-2- ethanaminebenzimidazole and the others are derivative of one 2-(chloromethyl)-1Hbenzo[d]imidazole, (1H-benzo[d]imidazol-2-yl)methanethiol and 2-(methoxymethyl)-1-methyl-1H-benzo[d]imidazole. The results from the antifungal screening were very interesting as there were 26 compounds, including two silver complexes, which were potent fungicides against the selected fungal species. They showed equivalent or greater potentency in their MIC values than amphotericin B. In particular, the 5-fluoro, 5-chloro and 5-bromo benzimidazole showed broad spectrum activity. / Saudi Culture Bureau and King Saud University

Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Salvia africana lutea is one of 26 Sage species indigenous to Southern Africa from a total of 900 worldwide. The genus Salvia belongs to the Lamiaceae family. Labeled a ‘broad spectrum remedy’ S. africana lutea amongst other sage species is medicinally important. Reports are many highlighting its benefits, which include from alleviating coughs and colds to gynaecological complaints. Studies have revealed in vitro antimicrobial, anti-cancer and antioxidant activity. Plant secondary metabolites fundamentally have a strong bearing on the phytochemical activities a plant may possess. Consequently the environment indirectly affects the phytochemical properties as it influences the variation in the plant metabolome via plant-environment interactions. Five S. africana lutea plant populations, within the Western Cape province of South Africa were sampled and chemotypes and bioactivity tested. Four populations were wild growing in protected areas namely; Brackenfell, Koeberg, Silwerstroomstrand and Yzerfontein, while the fifth was a garden growing population from Stellenbosch. Using gas chromatography hyphenated with mass spectrometry (GC-MS), compounds such as monosaccharides, carboxylic acids and fatty acids were detected. Variation of compounds identified with 80% certainty was compared across all populations. Stellenbosch population showed some compounds that were not present in the other four sites. These compounds were namely; propanoic acid, rythronic acid, 2-keto-1-gluconic acid and 1,3-dibromobicyclon, while this population also did not have xylitol that was detected in all the other four populations. To consolidate the GC-MS findings, analysis on the metabolite profiles (utilizing liquid chromatography linked with mass spectrometry (LC-MS) and nuclear magnetic resonance (1H NMR)) was done. Principal component analysis (PCA) was applied to the NMR data. The partial least squaresdiscriminant analysis (PLS-DA) was used to integrate LC-MS and NMR data sets. All statistics were performed with the SIMCA-P+ 12.0 software. By integrating LC-MS and 1H NMR analyses, large chemotype differences leading to samples grouping by site, suggested strong plant-environment interactions as factors influencing metabolite composition. Signals distinguishing the Stellenbosch profile were in the aromatic part of the 1H NMR spectra. Antimicrobial activity was tested against two Fusarium species. Fusarium is a plant pathogenic species that causes large agricultural losses particularly in the maize crop, one of the staple foods in the African continent. Some species also produce mycotoxins in infected crop and lead to a significant increase in the risk factor of cancers when contaminated foods are consumed. Four high-mycotoxin producing strains from two species F. verticillioides (MRC 826 and MRC 8267); F. proliferatum (MRC 7140 and MRC 6809) were utilized in all in vitro antifungal assays in this study. A preliminary assay using dichloromethane: methanol (1:1 v/v) crude plant extracts of the five populations; Stellenbosch, Brackenfell, Koeberg, Silwerstoomstrand and Yzerfontein, from 2009 and 2011. All test samples exhibited good activity as the minimum inhibitory concentrations (MIC) values ranged from 0.031 mg ml-1 to 0.5 mg ml-1, values below the latter are regarded as strong inhibitors. The Stellenbosch extracts were the most active for both 2009 and 2011 collections, with the best activity against F. verticillioides MRC 8267 and MRC 826 at 0.031 mg ml-1. While the least activity, albeit still a strong inhibitor, was observed from the Yzerfontein extracts with an MIC value of 0.5 mg ml-1. Generally comparison between the two years revealed that samples collected in 2011 were more potent than those in 2009, possibly due to prolonged storage that may have resulted in chemical decomposition. As the Stellenbosch population had shown the best activity as well as a relatively different chemical profile, leaves from these plants were then introduced into tissue culture conditions. Leaf explants were placed on solid plant growth regulator (PGR)-free Murashige and Skoog media and that supplemented with hormones in various combinations. (two concentrations of benzyl adenine (BA) utilized individually and in combination with naphthalene acetic acid (NAA) 4.4 and 8.8, while for NAA 0.27, 2.7 and 5.4.) Namely: 4.4 BA, 8.8 BA, 0.27 NAA: 4.4 BA, 2.7 NAA: 4.4 BA, 5.4 NAA: 4.4 BA, 2.7 NAA: 8.8 BA and 5.4 NAA: 8.8 BA. The PGR combinations did not induce shooting nor rooting, only callus on PGR-free MS media. Antifungal activity of the callus extract was in the same range as the whole plant extracts from which the leaf explants were harvested from, showing no ‘loss’ of activity after introduction to tissue culture conditions. Metabolite profiles using LC-MS, however, did reveal qualitative and quantitative differences, though they appear to not have any bearing on the activity. A bioassay-guided fractionation was then conducted on samples collected from Stellenbosch. This led to the identification of carnosol and carnosic acid being involved in the anti-Fusarium activity of S africana-lutea. A combinational study revealed no synergistic activity of the two compounds against four Fusarium test strains, with fractional inhibitory concentration (FIC) values of 1.5 and 3.0. Antifungal activity of carnosol and carnosic acid was observed to be in the same range (strong inhibitor) as was the callus and whole plant extracts. The study showed variation in population chemotypes and identified two compounds that are involved in S. africana-lutea activity against Fusarium species. It also provided a tissue culture system onto which mass production of the two bioactives may be achieved from, in the development of new fungicides. / AFRIKAANSE OPSOMMING: Salvia Africana lutea is een van die 26 Salie spesies wat inheems aan Suid-Afrika is uit ‘n totaal van 900 spesies wêreldwyd. Die genus Salvia hoort tot die Lamiaceae familie. S. africana lutea word geklassifiseer as ‘n “breë spektrum geneesmiddel”, en medisinaal as belangrik geag tussen die ander salie spesies, want volgens verslag word dit gebruik vir die verligting van hoes en verkoues tot selfs ginekologiese ongesteldhede. Definitiewe biologiese aktiwiteit eksperimente het anti-mikrobiese, antikanker en anti-oksidant aktiwiteite aan die lig gebring. Plant sekondêre metaboliete het fundamenteel ‘n baie sterk verband met die fitochemiese aktiwiteite van ‘n plant. Gevolglik affekteer die omgewing indirek die fitochemiese eienskappe, want dit beïnvloed die variasie in die plant metaboloom deur die interaksies van die plant met die omgewing. In vyf streke binne die Wes-Kaap van Suid-Afrika waar S. africana lutea bevolkings voorkom, is steekproewe gedoen en chemotipes en bioaktiwiteit getoets. Vier bevolkings was wild-groeiende bevolkings in beskermde areas, naamlik; Brackenfell, Koeberg, Silwerstroomstrand en Yzerfontein, terwyl die vyfde uit ‘n tuingroeiende bevolking in Stellenbosch geneem is. Deur gas chromatografie gekoppel met massa spektrometrie te gebruik, is primêre samestellings soos monosakkariede, karboksielsure en vetsure gevind. Variasies van samestellings wat met 80% sekerheid geïdentifiseer is, is oorkruis met al die bevolkings vergelyk. Die Stellenbosch bevolking het ‘n paar samestellings geopenbaar wat nie aanwesig was in die ander vier terreine nie. Hierdie samestellings was: propanoësuur, erythroniese suur, 2-keto-1-glukoniese suur en 1,3-dibromobicyclon. Verder het hierdie bevolking geen xylitol gehad nie en dit is in al vier die ander bevolkings gevind. Verdere studies was gedoen met die gebruik van vloeibare chromatografie gekoppel met massa spektrometrie (LC-MS) sowel as kern magnetiese resonansie (1H NMR). Chemiese profiele het hoë variasies getoon, en dus deur te fokus op die aromatiese samestelling streke, het die Stellenbosch terrein duidelik merkbare verskille en punte op die PLS-DA aangetoon. Met die koppeling van NMR data met LC-MS data, is daar gevind dat onderskeidende punte van die NMR PLS-DA wat gegroepeer is met retensie tye die skeiding van die Stellenbosch terrein van ander terreine gedryf het. Dit het onweerlegbaar bewys dat daar variasie binne die vyf bevolkings voorkom en dat Stellenbosch die mees noemenswaardige chemotipe variasie het. Dit blyk uit die anti-mikrobiese eksperimente dat aktiwiteit teen Fusarium heel nuwe belangstelling wek. Fusarium is ‘n plant-patogeniese spesie wat groot landbou verliese veroorsaak veral in die mielie gewasse, een van die stapelvoedsels van die Afrika kontinent. Dit produseer ook mikotoksiene in aangetaste gewasse en hierdie kan lei tot die ontstaan van kankers wanneer besmette voedsel op groot skaal verbruik word. Vier hoë-mikotoksien produserende swamlyne van twee spesies, naamlik F. verticillioides (MRC 826 en MRC 8267) en F. proliferatum (MRC 7140 en MRC 6809) is gebruik in alle in vitro anti-swam ondersoeke in hierdie studie. Die eerste analise het dichloromethan: methanol (1:1 v/v) ongesuiwerde plant ekstrakte bevat van die vyf bevolkings: Stellenbosch, Brackenfell, Koeberg, Silwerstroomstrand en Yzerfontein, geneem gedurende 2009 en 2011. Al hierdie toets monsters het goeie aktiwiteit getoon waar die minimum beperkende konsentrasie (MIC) waardes van 0.031 mg ml-1 tot 0.5 mg ml-1 gevarieer het. Waardes laer as laasgenoemde word beskou as sterk inhibeerders. Die Stellenbosch ekstrakte was die mees aktief vir albei jare hierbo genoem, met die beste aktiwiteit teen F. verticillioides MRC 8267 en MCR 826 by 0.031 mg ml-1. Die minste aktiwiteit (hoewel nog ‘n sterk inhibeerder) waargeneem was van die Yzerfontein ekstrakte, met ‘n MIC waarde van 0.5 mg ml-1. Oor die algemeen het ‘n vergelyking tussen die twee jare aangetoon dat die monsters wat in 2011 versamel is veel sterker was dan dié van 2009, moontlik te wyte aan ‘n verlengde bewaringstyd wat moontlik ‘n chemiese dekomposisie ten gevolge gehad het. Omdat die Stellenbosch bevolking die beste aktiwiteit getoon het sowel as ‘n relatief afwykende chemiese profiel, is blare van hierdie plante toe bekendgestel aan weefselkultuur kondisies. Blaar eksplante is op soliede hormoonvrye Murashige en Skoog media geplaas en dit is aangevul met sintetiese auksien Naftaleen asynsuur (NAA) en sitokien Bensiel adenien (BA) individueel en in verskillende kombinasies. Geen wortels of uitloopsels is waargeneem in al die hormoon kombinasies nie maar in die hormoonvrye media het daar egter Kallus in twintig persent van die eksplante voorgekom. Kallus is toe as subkultuur van hormoonvrye MS media gekweek en saamgevoeg en dichloromethan: methanol (1:1v/v) ekstrakte is getoets teen die volgende Fusarium swamlyne MRC 826; MRC 8267; MRC 7140 en MRC 6809. MIC waardes het sterk inhiberende eienskappe getoon met die laagste waarde as 0.025 mg ml-1 teen drie swamlyne: MRC 1740, MRC 8267 en MRC 826, en die hoogste was 0.25 mg ml-1 na 48 uur. Die minimum inhiberende konsentrasie waardes het gestyg na 0.5mg ml-1 na 60 uur, wat ‘n fungistatiese aksie getoon het. Maar van 60 tot 92 uu het waardes egter ‘n swamdodende aksie aangetoon met geen verandering van 0.5mg ml-1 nie. In die identifisering van die bioaktiewe komponente, is die ekstraksie van Stellenbosch se bevolking in dichloromethan: methanol (1:1 v/v) uitgevoer, en met gebruik van vyftig gram van die ekstrak is bioanalise-geleide fraksionering gedoen deur gebruik van ‘n VersaFlash®. Die mees aktiewe fraksie is verder gefraksioneer deur die gebruik van ‘n konvensionele silikajel kolom. Aktiewe fraksies is getoets deur LC-MS te gebruik, en twee verbindings, carnosol en carnosic suur, is geïdentifiseer. Voorbereidende TLC is gebruik om identiteit te bevestig, want fraksies was naas die kommersiele standaarde van die twee verbindings getoets. Sinergistiese aktiwiteit van die twee samestellings is ondersoek deur ‘n antiswam ontleding teen die vier swamlyne uit te voer. Hierdie studie het dus die veronderstelde bestaan van verskillende chemotipes tussen die bevolkings waarvan voorbeelde geneem is, bekend gestel. Veral die Stellenbosch se bevolking het die meeste verskil, heel moontlik omrede die verlengde en hoër versteurings deur die nabyheid van mense. Plant– omgewing interaksies speel ‘n belangrike rol in die metaboloom van plante, wat dan indirek hul eienskappe verander, en in hierdie geval die antiswam aktiwiteit. Die tuingroeiende bevolking was die mees aktief, heel moontlik omrede hierdie aspek. Nietemin was geen bioaktiwiteit verloor waar die mees kragtige bevolking met weefsel kultuur kondisies in aanraking gebring is nie. Dus is dit ideaal vir kommersialisering. Een nuwe belangrike bevinding was die carnosol en carnosic suur wat twee welbekende samestellings is wat meesal geassosieer is met Rosmarinus officinalis en gedokumenteer is vir antioksidant aktiwiteit. Hier dui laasgenoemde samestellings ‘n antiswam aktiwiteit aan teen die getoetste Fusarium swamlyne. Met ‘n gevestigde weefsel kultuur sisteem alreeds in plek, voorsien dit ‘n beginpunt vir die bestudering van hoe hierdie bioaktiewe komponente in massa geproduseer kan word in die ontwikkeling van nuwe swamdodende produkte.

Une grande variété de curcuminoïdes Cs et de tétrahydrocurcuminoïdes THCs a été synthétisée et leurs propriétés antioxydantes ont été étudiées en détail par la méthode du radical DPPH°. Pour la première fois, il a été montré que les propriétés antioxydantes supérieures des THCs par rapport à leurs homologues curcuminoïdes sont dues à la présence d’atomes d’hydrogène benzyliques dans les THCs. L’association de THCs avec un biopolymère, le chitosane, a permis l’élaboration de films à propriétés antioxydantes et antibactériennes. Des interactions entre les THCs et le chitosane ont été mises en évidence par spectroscopie d’absorption UV-visible. Les THCs et plus particulièrement la tétrahydrocurcumine, se sont révélés capables à la fois d’inhiber le développement de Fusarium proliferatum, champignon qui s’attaque aux céréales, et de limiter la production de mycotoxines issues de cette souche. / A large variety of curcuminoids Cs and tetrahydrocurcuminoids THCs was synthesized and their antioxidant properties were studied in detail by the radical DPPH° method. For the first time, it was shown that the higher antioxidant properties of THCs compared to their counterparts’ curcuminoids are due to the presence of benzylic hydrogen atoms in THCs. The association of THCs with a biopolymer chitosan, allowed the preparation of films presenting antioxidant and antibacterial properties. Interactions between THCs and chitosan were evidenced by UV-visible absorption spectroscopy. THCs and more particularly tetrahydrocurcumin inhibited development of Fusarium proliferatum fungi in cereals, and limited the production of associated mycotoxins.