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, 21β-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 21β-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 (SI_Dd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21β-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21β-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.

The investigation of the methanol extract of the flowers of Jacaranda mimosifolia led to the isolation and characterisation of fourteen secondary metabolites (1-14) by the means of chromatographic and spectroscopic analysis. These compounds include eight flavonoids sorted as two flavonols (1-2), three flavones (3, 7-8), and three isoflavones (4, 9-10), two glucoiridoids (5-6), and four triterpenoids sorted as one oleanane (11), one hopane (12), and two lupane (13-14). The in vitro antioxidant potential of all the isolated compounds was evaluated using the ABTS- and FRAP- methods, which demonstrated concentration-dependent activity. Chloroflavonin A (1) and 4',5,7-trihydroxyflavone (2) demonstrated exceptional antioxidant activity, with scavenging rates of 98.63 % and 97.89 %, respectively, at a concentration of 300 μg/mL, and also showed strong ferric-reducing antioxidant power. Chloroflavonin A (1) demonstrated the most potent dual inhibitory effects on Cyclooxigenase-2 (COX-2) and NADPH-Oxidase-5 (NOX-5) enzymes, with binding affinities of -9.7 and -8.2 kcal/mol, respectively, indicating its potential as a strong anti-inflammatory compound. The molecular dynamics simulation, conducted with the Desmond v3.6, demonstrated the stability of the various complexes within the biological system. The findings indicate that compounds derived from Jacaranda mimosifolia may serve as potential therapeutic agents for the management of inflammation and oxidative stress.

One new tirucallan derivative, leutcharic acid (1) was isolated from Stereospermum acuminatissimum stem bark together with the known compounds 3-oxo-22-hydroxyhopane (2), 3,4-secotirucalla-4(28),7,24-trien-3,21-dioic acid (3), 3-oxotirucalla-7,24-dien-21-oic acid (7), lupeol (4), β-sitosterol (5) and stigmasterol (6). The structures of the isolated compounds were elucidated using 1 D and 2 D NMR spectroscopy in combination with literature data. To the best of our knowledge, this is the first report on the cytotoxic properties’ constituents of S. acuminatissimum. Cytotoxicity of compounds 1 and 2 was assessed in vitro with the WST-1 assay on human lung adenocarcinoma A549 and THP-1 human monocytic leukaemia cell lines. Both compounds showed antiproliferative activity on the cancer cells. Compound 2 was more active against THP-1 with an IC₅₀ value of 26.83 µM. The sensitivity of THP-1 cells to compounds 1 and 2 indicated that these compounds might be potential leads for anticancer agent development against leukaemia.

Twenty-two compounds were isolated from the fruit of Albizia lebbeck including one unprecedented, rare amino acid-derived zwitterionic and one new flavone derivative. The isolation was performed on repeated column chromatography over silica gel and their structures were determined by 1D-, 2D-NMR and HR-ESI-MS spectra together with reported data in the literature. The chemophenetic significance is also discussed. Some isolated compounds were reported for the first time to be found in the species. Additionally, compound 2 showed antibacterial activity and compounds 1 and 2 revealed moderate cytotoxic activity against the Raw 264.7 cancer cell line with IC₅₀ values of 37.19 µM and 29.36 µM, respectively. Furthermore, a proposed biosynthetic pathway of compound 1 is described.

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-β-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. Graphical Abstract