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.

Antimicrobial and Cytotoxic Activities of Constituents from the Fruit of Albizia lebbeck L. Benth (Fabaceae).

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.

Antibacterial and Antioxidant Activities of Isolated Compounds from Prosopis africana Leaves.

Prosopis africana (G. &Perr.) Taub (Mimosaceae) is a large tree native to dry tropical Africa and characteristic of dry leguminous forests. Different parts of this plant are used to treat wounds, skin infection, and to fight against cancer. Literature review indicated various pharmacological properties. Despite these medicinal properties, the chemical composition studies remain limited. This study aims to isolate and characterize secondary metabolites from P. africana leaves and evaluate their antibacterial and antioxidant properties. Air-dried powdered leaves of P. africana were macerated in methanol at room temperature and partitioned with ethyl acetate. The EtOAc extract was subjected successively to flash and column chromatographies in order to isolate compounds. The structure of the isolates was determined with help of spectroscopic data including 1D and 2D NMR experiments and comparison with literature data. The antibacterial activities were evaluated via determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antioxidant activities were evaluated via gallic acid equivalent antioxidant capacity (GEAC) and diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. The chemical investigation of the EtOAc extract led to the isolation of seven compounds: (2E, 6E) farnesylamine (1), myricetin-3-O-rhamnoside (2), bis(2-ethylhexyl) benzene-1,2-dicarboxylate (3), lupeol (4), ß-sitosterol (5), stigmasterol glycoside (6), and a mixture of bis(2-ethylhexyl) benzene-1,2-dicarboxylate (3) and bis(2-ethylhexyl) benzene-1,4-dicarboxylate (7) in ratio 1 : 2. Compound 1 is described here for the first time as a natural product with complete 1H and 13C assignments. Compounds 3 and 7 were identified as artefacts from dichloromethane. Sesquiterpene amine (1) is reported in Prosopis genus for the first time. Antibacterial and antioxidant activities of isolated compounds were investigated. Among the tested samples, the EtOAc extract and compound 2 exhibited the highest antioxidant (EC50 = 5.67-77.56 µg/mL; GEAC = 36.58-89.28 µg/mL) and antibacterial (MIC = 8-64 µg/mL) activities against gram-negative and gram-positive bacteria. The EtOAc extract and compound 2 from P. africana exhibited antibacterial activity through bacteriolytic effects and reduction of the antioxidant defenses in the bacterial cells. Furthermore, the chemotaxonomic significance of isolated compounds was discussed. The antibacterial and antioxidant activities of ethyl acetate extract and compound 2 can justify the traditional uses of P. africana leaves for the treatment of diseases related to bacterial infections. The presence of compounds 1, 2, and 4 in this plant should also be considered as valuable chemotaxonomic features.

Cytotoxicity of a new tirucallane derivative isolated from Stereospermum acuminatissimum K. Schum stem bark.

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), ß-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.

Lambertellin from Pycnoporus sanguineus MUCL 51321 and its anti-inflammatory effect via modulation of MAPK and NF-κB signaling pathways.

Lambertellin (1) and ergosta-5,7,22-trien-3-ol (2) were isolated from the solid rice fermentation of the plant pathogenic fungus Pycnoporus sanguineus MUCL 51321. Their structures were elucidated using comprehensive spectroscopic methods. The isolated compounds were tested on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Lambertellin (1) exhibited promising inhibitory activity against nitric oxide (NO) production with IC50 value of 3.19 µM, and it significantly inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Lambertellin (1) also decreased the expression of pro-inflammatory cytokines IL-6 and IL-1ß. The study of the mechanistic pathways revealed that lambertellin (1) exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophage cells by modulating the activation of the mitogen activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. Therefore, lambertellin (1) could be a promising lead compound for the development of new anti-inflammatory drugs.

Isolation and biological activity of compounds from Garcinia preussii.

CONTEXT: Plants of the genus Garcinia (Clusiaceae) are traditionally used to relieve stomachaches, toothaches, and as a chew stick. OBJECTIVE: In order to determine which compounds were responsible for these activities, a phytochemical investigation of the fruits and leaves of Garcinia preussii Engl. was pursued. MATERIALS AND METHODS: Plants were extracted by solvents of various polarities. Compounds isolation was then carried out using chromatography methods (medium- and high-pressure liquid chromatography, open column and thin-layer chromatography). The isolated compounds were identified and characterized by using 1D and 2D NMR spectroscopies. The antioxidant activity was evaluated using DPPH(•), ABTS(•-), ALP, and ORAC assays. The antimicrobial activity was assayed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis by determining the minimum inhibitory concentration (MIC) value. The cytotoxic activity of most of the isolated compounds was evaluated on a small panel of human cancer cell lines (DU145, HeLa, HT-29, and A431) using the XTT method. RESULTS: The phytochemical investigation of G. preussii led to the isolation of eight known compounds, six benzophenones and two flavonoids. These compounds were tested for their biological activities. 1, 2, 3, 4, 7 and 8 demonstrated a high free radical scavenging activity with ER50 ranging from 0.1 to 0.7. The antimicrobial activity was shown only against Gram-positive bacteria for 1, 4, and 5. A moderate cytotoxic activity with IC50 ranging from 7 to 50 µM was observed, except for 6 which was not active. CONCLUSION: These results appear to support some of the properties reported for Garcinia species.