Bathelemy Ngameni

Cancer is a leading cause of death worldwide, and chemotherapy is facing challenges ranging from side effects, selectivity, and resistance. Molecules from nature are a prolific source of anticancer molecules. This study aimed to discover new anticancer molecules from Gambeya lacourtiana stem bark extract using in vitro assays. Complete assignment of the NMR data of 3, 5, 7, 3 ' , 5 ' ‐pentahydroxy‐4 ' ‐methoxyflavane or 4 ' ‐methoxyepigallocatechin ( 1 ) isolated from the stem bark of G. lacourtiana along with (‐)‐epicatechin ( 2 ),  β ‐amyrin pentanoate ( 3 ), α ‐amyrin acetate ( 4 ), lupeol acetate ( 5 ), taraxerol ( 6 ), 28‐hydroxyl‐3 β ‐amyrin ( 7 ), euscaphic acid ( 8 ), betulinic acid ( 9 ), chondrillasterol ( 10 ), and 3‐ O ‐ β ‐D‐glucopyranosyl chondrillasterol ( 11 ) was achieved. Structures were elucidated by the interpretation of their NMR and spectrometric data in conjunction with literature data. In vitro cytotoxicity carried out on isolates toward CCRF‐CEM revealed only compound 1 to be moderately cytotoxic (IC ₅₀ = 29.45 µg/mL). PASS analysis suggested that the isolated compounds had antineoplastic, antiproliferative, anti‐inflammatory, hepatoprotective, chemopreventive, membrane integrity agonist, mucomembranous protector, insulin promoter, fibrinolytic, and antioxidant effects. In addition, isolates were projected to treat hepatic disorders, leishmaniasis, wounds, proliferative diseases, capillary fragility, hypercholesterolemia, influenza, eczema, and leukemia. Predictions on its inhibition of testosterone 17 β ‐dehydrogenase (NADP+), a key enzyme involved in androgen metabolism, corroborate the use of this plant traditionally to solve reproductive health issues.

A new Lanosta-7,9(11),22-trien-3,15,20-triol named Anomanol B 1, together with five known compounds: manniindole 2, arborinine 3, polycarpol 4, 8,9-dimethoxyphenanthridin-6(5H)-one 5 and 3-O-& beta;-D-glucopyranosyl-& beta;-sitosterol 6 were isolated from the stem bark extract of Anonidium mannii by routine chromatography techniques. 8,9-dimethoxyphenanthridin-6(5H)-one 5, was reported from natural origin for the first time. The structures of the compounds were established by comprehensive elucidation of spectroscopic data and by comparison with literature data. Evaluation of the isolates on Gram-negative bacteria such as Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Providencia stuartii, and Pseudomonas aeruginosa showed that, compound 1 had weak antibacterial activity with minimal inhibitory concentrations (MIC) varying from 128 to 256 & mu;g/mL. Compounds 3, 5, and 6 exhibited moderate to weak activity with MIC of 32 to 128 & mu;g/mL and 64 to 256 & mu;g/mL compared to the reference drug chloramphenicol which inhibited the growth of all studied bacteria with MIC values of 16 to 64 & mu;g/mL.

Background: The rise of multidrug-resistant (MDR) bacteria is a real public health problem worldwide and is responsible for the increase in hospital infections. Donella welwitschii is a liana or shrub belonging to the family Sapotaceae and traditionally used to cure coughs. Objective: This study was conducted with the objective to validate the medicinal properties of this plant, the aerial part was studied for its phytochemical composition using column and PTLC chromatography and exploring its antibacterial and antibiotic-modifying activity as well as those of its phytochemicals. Methods: The structures of the compounds were elucidated from their physical and spectroscopic data in conjunction with literature. The antibacterial activity of the isolated metabolites was performed toward a panel of MDR Gram negative and Gram-positive bacteria. The broth micro-dilution method was used to determine antibacterial activities, efflux pump effect using the efflux pump inhibitor (EPI) (phenylalanine-arginine-ß-naphthylamide (PAβN)), as well as the modulating activity of antibiotics. Monitoring the acidification of the bacterial growth medium was used to study the effects of the samples on the bacterial proton-ATPase pumps and cellular ATP production. Results: Eleven compounds were isolated including pentacyclic triterpenes, C-glucosyl benzophenones. With a MIC value < 10 μg/mL, diospyric acid (7) significantly inhibited the growth of Escherichia coli AG102, Enterobacter aerogenes ATCC13048, Klebsiella pneumoniae KP55, Providencia stuartii NEA16 and Staphylococcus aureus MRSA3. 28-hydroxy-β-amyrin (8) significantly impaired the growth of Enterobacter aerogenes EA27, Klebsiella pneumoniae ATCC11296 and Staphylococcus aureus MRSA6; and oleanolic acid (9) strongly impaired the growth of Escherichia coli AG 102, Enterobacter aerogenes EA27 and Providencia stuartii PS2636. Diospyric acid (7) and 28-hydroxy-β-amyrin (8) induced perturbation of H⁺-ATPase pump and inhibition of the cellular ATP production. Moreover, at MIC/2 and MIC/4, compounds 7, 8, and 9 strongly improved the antibacterial activity of norfloxacin, ciprofloxacin and doxycycline with antibiotic-modulating factors ranging between 2 and 64. Conclusion: The overall results of the current work demonstrate that diospyric acid (7), 28-hydroxy-β-amyrin (8) and oleanolic acid (9) are the major bioactive constituents of Donella welwitschia towards Gram-negative bacteria expressing MDR phenotypes.

Agelanthus brunneus (Loranthaceae) is a hemiparasitic plant growing on Senna siamea (Fabaceae). The chemical investigation of its leaves and flowers led to the isolation of one new phenolic compound namely (−)-brunneusine (1), together with 13 known compounds. The crude leaves and flowers extracts (CLE and CFLE) with their ethyl acetate fractions (EAFL and EAFFL) and some isolated compounds (1–3; 8–9 and 11–14) have been tested on four bacterial species of sanitary importance isolated in an aquatic environment. All the samples except compound 3 showed antibacterial activity with MICs ranging from 0.43 to 8.88.10³ µg/mL and MBCs from 0.43 to 3.55.10³ µg/mL. Compounds 9 and 14 showed better activity on all bacterial species tested with MICs ranging from 0.43 to 27.77 µg/mL. Only CLE, EAFL and compounds 14, 2, 8 and 9 showed bactericidal effects on all bacterial species tested.

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 OD_{600 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.

A series of novel 4- O -alkyltriazolylphenolic derivatives is first synthesized with good to excellent yields via the click reaction of 3-methoxy-4- O -propargylbenzaldehyde or 3-allyl-4- O -propargylacetophenone and aromatic azide derivatives. Next, the chalcones are prepared via the Claisen-Schmidt method from 4- O -alkylphenylketone derivatives in the presence of the corresponding (hetero)aromatic aldehydes as electrophiles. The structures of the newly synthesized compounds are confirmed from their infrared, nuclear magnetic resonance spectral data, and by elemental analysis. The main advantages of this procedure are the simplicity of the reaction conditions, easily available starting materials, and simple work-up. The antioxidant activity of several of the products is determined using the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) radical scavenging assay. 4- O -propargylvanillin (IC ₅₀ = 14.54 µg/mL) had moderate antioxidant activity.

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 (GI₅₀) 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 GI₅₀ values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI₅₀ 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 GI₅₀ 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.

The chemical investigation of the leaves and stem bark of Acacia polyacantha (Fabaceae) led to the isolation of a new oleanane-type triterpenoid saponin named polyacanthoside A 1 together with fifteen known compounds. Their structures were established from spectral , mainly HRESIMS, 1D NMR and 2D NMR and by comparison with literature data. The cytotoxicity of compound 1 and the analogues 8 as well as doxorubicin was determined in a panel of 9 cancer cell lines including sensitive and drug resistant phenotypes. Unlike the analogue 8, compound 1 as well as doxorubicin displayed cytotoxic effects in all the 9 tested cancer cell lines with IC₅₀ values ranged from 8.90 μM (towards CCRF-CEM leukemia cells) to 35.21 μM (towards HepG2 hepatocarcinoma cells) for compound 1 and from 0.02 μM (towards CCRF-CEM leukemia cells) to 66.83 μM (against CEM/ADR5000 leukemia cells) for doxorubicin.