Synthesis of novel stilbene–coumarin derivatives and antifungal screening of monotes kerstingii-specialized metabolites against fusarium oxysporum

Fusarium is one of the most toxigenic phytopathogens causing diseases and reduced agricultural productivity worldwide. Current chemical fungicides exhibit toxicity against non-target organisms, triggering negative environmental impact, and are a danger to consumers. In order to explore the chemical diversity of plants for potential antifungal applications, crude extract and fractions from Monotes kerstingii were screened for their activity against two multi-resistant Fusarium oxysporum strains: Fo32931 and Fo4287. Antifungal activity was evaluated by the determination of minimum inhibitory concentration (MIC) by broth dilution of fermentative yeasts using kinetic OD600 nm reading by a spectrophotometer. The n-butanol fraction showed the best activity against Fo4287. We screened eleven previously reported natural compounds isolated from different fractions, and a stilbene–coumarin 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-4,7-dimethoxy-3-methyl-2H-1-benzopyran-2-one (1) was the most active compound against both strains. Compound 1 was employed as a nucleophile with a selection of electrophilic derivatizing agents to synthesize five novel stilbene–coumarin analogues. These semisynthetic derivatives showed moderate activity against Fo32931 with only prenylated derivative exhibiting activity comparable to the natural stilbene–coumarin (1), demonstrating the key role of the phenolic group

In vitro antifungal activity of Dorstenia mannii leaf extracts (Moraceae)

The leaves of Dorstenia mannii are used in traditional medicine in Cameroon and other African countries for the treatment of infectious diseases like malaria, skin rashes and stomach disorders. To substantiate this folkloric claim, the crude methanol extract and fractions from the leaves of D. mannii were investigated for their antifungal activity. The crude methanol extract was prepared from powdered dried leaves of the D. mannii. A portion was subjected to flash liquid chromatography on silica gel to afford test fractions. All test samples were screened for major groups of phytochemicals.Test samples and nystatin (reference) were evaluated for antifungal activity on ten yeasts using agar disc diffusion and broth microdilution methods. The qualitative analysis of crude methanol extract and fractions of D. mannii leaves revealed the presence of flavonoids, phenols, steroids and cardiac glycosides. In agar disc diffusion assay, seven of the ten pathogenic fungal strains were sensitive to the crude methanol extract (7/10), n-hexane ethyl-acetate (Hex-EA) (75%) (8/10) and ethyl-acetate (100%) (8/10). The minimum inhibitory concentrations (MICs) for the test samples varied from 80 to 1280 μg/ml. The crude extract and ethyl-acetate (100%) were the most active plant samples with both fungistatic and fungicidal effects (MIC/MFC values from 80 to 640 μg/ml) though not as the reference drug. Candida tropicalis was the least sensitive to the test samples. Some fractions exerted no fungicidal actions on Cryptococcus neoformans, Candida lusitaniae and Candida tropicalis. The present work shows that the crude methanol extract and fractions (n-hexane, ethyl acetate and residue) from the leaves of D. mannii possess growth inhibitory effect on pathogenic yeast. The active ingredients of this plant could be an addition to the antifungal arsenal to opportunistic fungal yeast pathogens.Keywords: Antifungal activity, Dorstenia mannii, yeasts, opportunistic candidiasi

Antihepatotoxic and Antioxidant Activities of Methanol Extract and Isolated Compounds from Ficus chlamydocarpa

Free radicals, in particular radical oxygen species (ROS), play an important role in the aetiology and pathogenesis of various diseases. Current research in many countries focuses on the use of local medicinal plants as a promising source of liver protective agents. This paper describes the hepatoprotective effects of the methanol extract and four isolated compounds from Ficus chlamydocarpa on CCl4-induced liver damage, as well as the possible antioxidant mechanisms involved in this protection. The DPPH test, along with the ß-Carotene-Linoleic Acid Model System and Ferric-Reducing Antioxidant Power assays, as well as the inhibition of microsomal lipid peroxidation were used to measure radical-scavenging and antioxidant activities. Pretreatment of rats with the methanol extract of F. chlamydocarpa before CCl4administration, significantly prevented serum increase of hepatic enzyme markers, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), in a dose-dependent manner. The hepatoprotection was also associated with a significant enhancement in hepatic reduced glutathione (GSH) and a marked decrease of liver malondialdehyde (MDA). Among the four compounds 1-4, isolated from the methanol extract, α-amyrin acetate (1) and luteolin (4) showed a significant hepatoprotective activity, as indicated by their ability to prevent liver cell death and lactate dehydrogenase (LDH) leakage during CCl4intoxication

Trypanocidal and leishmanicidal activity of six limonoids

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1–4 displayed anti-leishmanial activity. The 50% growth inhibition (GI 50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI 50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI 50 values of 100 μM and 31.5–46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI 50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis

<b>Prenylated and geranylated chalcones and flavones from the aerial parts of <i>Dorstenia ciliata</i></b>

Investigation of the aerial parts of Dorstenia ciliata yielded two new prenylated flavones named ciliatins A and B and characterized as 6,7-(2’’-isopropenyldihydrofurano)-5,4’-dihydroxyflavone and 6,5-(2,2-dimethyldihydropyrano)-7,4’-dihydroxy-3’-methoxyflavone, respectively. Known flavonoids: stipulin, isobavachalcone, licoflavone C, 6-prenylapigenin, dinklagin C, gancaonin P, canniflavone and poinsettifolin A were also identified. Structures of these secondary metabolites were established on the basis of spectroscopic analysis, comparison with published information and with authentic specimen for some cases and chemical evidence for the dihydropyranoflavone derivative

In vitro antifungal activity of Dorstenia mannii leaf extracts (Moraceae)

The leaves of Dorstenia mannii are used in traditional medicine in Cameroon and other African countries for the treatment of infectious diseases like malaria, skin rashes and stomach disorders. To substantiate this folkloric claim, the crude methanol extract and fractions from the leaves of D. mannii were investigated for their antifungal activity. The crude methanol extract was prepared from powdered dried leaves of the D. mannii. A portion was subjected to flash liquid chromatography on silica gel to afford test fractions. All test samples were screened for major groups of phytochemicals.Test samples and nystatin (reference) were evaluated for antifungal activity on ten yeasts using agar disc diffusion and broth microdilution methods. The qualitative analysis of crude methanol extract and fractions of D. mannii leaves revealed the presence of flavonoids, phenols, steroids and cardiac glycosides. In agar disc diffusion assay, seven of the ten pathogenic fungal strains were sensitive to the crude methanol extract (7/10), n-hexane ethyl-acetate (Hex-EA) (75%) (8/10) and ethyl-acetate (100%) (8/10). The minimum inhibitory concentrations (MICs) for the test samples varied from 80 to 1280 μg/ml. The crude extract and ethyl-acetate (100%) were the most active plant samples with both fungistatic and fungicidal effects (MIC/MFC values from 80 to 640 μg/ml) though not as the reference drug. Candida tropicalis was the least sensitive to the test samples. Some fractions exerted no fungicidal actions on Cryptococcus neoformans, Candida lusitaniae and Candida tropicalis. The present work shows that the crude methanol extract and fractions (n-hexane, ethyl acetate and residue) from the leaves of D. mannii possess growth inhibitory effect on pathogenic yeast. The active ingredients of this plant could be an addition to the antifungal arsenal to opportunistic fungal yeast pathogens.Key words: Antifungal activity, Dorstenia mannii, yeasts, opportunistic candidiasis

Antimicrobial activities of the methanol extract, fractions and compounds from <it>Ficus polita </it>Vahl. (Moraceae)

Abstract Background Many plants of the family Moraceae are used in the treatment of infectious diseases. Ficus polita Vahl., an edible plant belonging to this family is used traditionally in case of dyspepsia, infectious diseases, abdominal pains and diarrhea. The present work was designed to assess the antimicrobial activity of the methanol extract from the roots of F. polita (FPR), as well as that of its fractions (FPR1-5) and two of the eight isolated compounds, namely euphol-3-O-cinnamate (1) and (E)-3,5,4'-trihydroxy-stilbene-3,5-O-β-D-diglucopyranoside (8). Methods The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species. Results The results of the MIC determination showed that the crude extract, fractions FPR1, FPR2 and compound 8 were able to prevent the growth of the eight tested microorganisms. Other samples showed selective activity. The lowest MIC value of 64 μg/ml for the crude extract was recorded on 50% of the studied microbial species. The corresponding value for fractions of 32 μg/ml was obtained on Salmonella typhi, Escherichia coli and Candida albicans ATCC strains. The MIC values recorded with compound 8 on the resistant Pseudomonas aeruginosa PA01 strain was equal to that of chloramphenicol used as reference antibiotic. Conclusion The obtained results highlighted the interesting antimicrobial potency of F. polita as well as that of compound 8, and provided scientific basis for the traditional use of this taxon in the treatment of microbial infections.</p