In vitro and in silico assessment of antidiabetic and antioxidant potencies of secondary metabolites from Gymnema sylvestre.

This study investigated the chemical constituents, antioxidant potential, and in vitro and in silico antidiabetic activity of Gymnema sylvestre. Column chromatography and spectroscopic techniques identified twelve compounds from the methanol extract, including 4 sterols (1-4), 5 triterpenoids (5-9), and 3 flavonoids (10-12). The chemophenetic significance of all compounds was also investigated. The antioxidant capacity of the extract and compounds (1-4) was evaluated using FRAP and DPPH assays. The extract exhibited strong free radical scavenging activity (IC50 = 48.34 µg/mL), while compounds (1-4) displayed varying degrees of efficacy (IC50 = 98.30-286.13 µg/mL). The FRAP assay indicated significant reducing power for both extract and compounds (58.54, 47.61, 56.61, and 49.11 mg Eq.VitC/g for extract and compounds 1 & 2, 3, and 4, respectively). The antidiabetic potential was assessed through α-amylase and α-glucosidase enzyme inhibition assays. The crude extract demonstrated the most potent inhibition (IC50 = 218.46 and 57.42 µg/mL for α-glucosidase and α-amylase respectively) suggesting its potential for managing postprandial hyperglycaemia. In silico studies employed molecular docking and dynamics simulations to elucidate the interactions between identified compounds and α-amylase/α-glucosidase enzymes. The results revealed promising binding affinities between the compounds and target enzymes, with compound 6 demonstrating the highest predicted inhibitory activity with -10 kcal/mol and -9.1 kcal/mol for α-amylase and α-glucosidase, respectively. This study highlights the presence of diverse bioactive compounds in Gymnema sylvestre. The extract exhibits antioxidant properties and inhibits carbohydrate-digesting enzymes, suggesting its potential as a complementary therapeutic approach for managing hyperglycaemia associated with type 2 diabetes.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

A new flavonol derivative and other compounds from the leaves of Bauhinia thonningii Schum with activity against multidrug-resistant bacteria.

Investigation of the leaves of Bauhinia thonningii Schum led to the isolation and identification of a new flavonol derivative, 6-C-methylquercetin-3,4'-dimethyl ether (1) together with eleven known compounds (2-13), with two of them (10 and 11) obtained as a mixture. Their structures were established by extensive spectroscopic analyses. Antibacterial activity of compound 1 as well as the reference antibiotic, ciprofloxacin was tested on Gram-negative multidrug-resistant bacteria overexpressing active efflux pumps, and against methicillin-resistant strains of Staphylococcus aureus (MRSA). Samples were tested alone and in combination with an efflux pump inhibitor (EPI), phenylalanine-arginine-ß-naphthylamide (PAßN). Results show that when compound 1 was tested alone, its inhibitory effects were obtained on 7/10 tested bacteria with the highest MIC value of 128 µg/mL whilst in the presence of EPI, this activity significantly increase in all the 10 bacteria. An interesting antibacterial activity was obtained with compound 1 against Klebsiella pneumoniae ATCC11296 (MIC of 4 µg/mL), KP55 and Staphylococcus aureus MRSA6 in the presence of the PaßN.

Antibacterial and antioxidant activities and phytochemical composition of Stereospermum kunthianum root bark.

A new glycoiridoid (1) together with seven (7) known compounds were isolated from the methanol crude extract of the root bark of Stereospermum kunthianum using chromatography methods. Their structures were elucidated using HR-ESI-MS, 1 D- & 2 D-NMR spectroscopies in comparison with previous literature. The antioxidant activity was investigated by using FRAP, DPPH, ABTS and HRSA methods while the antibacterial activity was assays on Escherichia coli (ATCC25922) and Salmonella typhimurium (ATCC14028) strains. The results showed that the isolated compounds had significantly (p < 0.01) high radical scavenging (IC50) and reducing power activity. All bacteria strains showed important minimal inhibitory concentration activity against isolated compounds started at 5 mg/mL with an inhibition zone of 6 mm. Thus, the isolated compounds in S. kunthianum justify the use of the plant in traditional medicine for the treatment of various diseases in humans. These isolated compounds can be used for formulation of new drug discovery to treat infectious diseases.