Screening of the Pan-African Natural Product Library Identifies Ixoratannin A-2 and Boldine as Novel HIV-1 Inhibitors

The continued burden of HIV in resource-limited regions such as parts of sub-Saharan Africa, combined with adverse effects and potential risks of resistance to existing antiretroviral therapies, emphasize the need to identify new HIV inhibitors. Here we performed a virtual screen of molecules from the pan-African Natural Product Library, the largest collection of medicinal plant-derived pure compounds on the African continent. We identified eight molecules with structural similarity to reported interactors of Vpu, an HIV-1 accessory protein with reported ion channel activity. Using in vitro HIV-1 replication assays with a CD4+ T cell line and peripheral blood mononuclear cells, we confirmed antiviral activity and minimal cytotoxicity for two compounds, ixoratannin A-2 and boldine. Notably, ixoratannin A-2 retained inhibitory activity against recombinant HIV-1 strains encoding patient-derived mutations that confer resistance to protease, non-nucleoside reverse transcriptase, or integrase inhibitors. Moreover, ixoratannin A-2 was less effective at inhibiting replication of HIV-1 lacking Vpu, supporting this protein as a possible direct or indirect target. In contrast, boldine was less effective against a protease inhibitor-resistant HIV-1 strain. Both ixoratannin A-2 and boldine also inhibited in vitro replication of hepatitis C virus (HCV). However, BIT-225, a previously-reported Vpu inhibitor, demonstrated antiviral activity but also cytotoxicity in HIV-1 and HCV replication assays. Our work identifies pure compounds derived from African plants with potential novel activities against viruses that disproportionately afflict resource-limited regions of the world

ISOLATION AND CHARACTERIZATION OF CHEMICAL CONSTITUENTS FROM Chrysophyllum albidum G. DON-HOLL. STEM-BARK EXTRACTS AND THEIR ANTIOXIDANT AND ANTIBACTERIAL PROPERTIES

Background: The plant, Chrysophyllum albidum is indigenous to Nigeria and its stem-bark has found relevance in folkloric medicine for infections and oxidative stress linked diseases medicaments. The study targets to isolate the chemical constituents accountable for the antioxidant and antibacterial actions of the plant stem-bark to substantiate some of its ethnomedicinal uses. Materials and Methods: Stem-bark extract of Chrysophyllum albidum was obtained from 80 % ethanol was partitioned in sequence with ethyl acetate (EtOAc) and n-butanol. The solvent fractions and isolated compounds were verified for antioxidant chattels utilizing 2-2-diphenyl-1-picrylhydrazyl. Antibacterial actions were also assessed by agency of agar-diffusion and broth micro dilution methods. EtOAc fraction was on many occasions chromatographed on silica and Sephadex LH-20 column to afford four compounds and their chemical structures were proven with the employment of NMR (1D and 2D) and MS. Results: Chromatographic fractionation of EtOAc fraction with the premier antioxidant and antimicrobial activities afforded stigmasterol (1), epicatechin (2), epigallocatechin (3) and procyanidin B5 (4). Procyanidin B5 isolated for the first time from Chrysophyllum genus proven the supreme antioxidant activity with IC50 values of 8.8 µM and 11.20 µM in DPPH and nitric oxide assays respectively and equally established the ultmost inhibitory activity against Escherichia coli (MIC 156.25 μg/mL), Staphylococcus aureus (MIC 156.25 μg/mL), Pseudomonas aeruginosa (MIC 625 μg/mL) and Bacillus subtilis (MIC 156.25 μg/mL). Conclusion: The antibacterial and antioxidant activities of epicatechin, epigallocatechin and procyanidin B5 isolated from Chrysophyllum albidum stem-bark substantiate the folkloric use

THE EFFECTS OF SOME SYNTHESISED STILBENE ANALOGUES ON ARTEMIA SALINA NAUPALII AND GERMINATION OF SORGHUM BICOLOR SEEDS

Six stilbene and their corresponding bibenzyl alcohols with no substitution on one ring were synthesized via the Grignard route. Corresponding dihydrostilbenes were obtained by transfer hydrogenation of the stilbenes. Dihydropinosylvin, the major phytoalexin in Dioscorea species was obtainend by demethylation of 3,5 dimethoxybibenzyl. P-Hydroxystilbene (LC50 1.0mg/ml), m-hydroxy stilbene (LC501.48) and 4-methoxy stilbene (LC508.0) were the most toxic to A. salina nauplii followed by their respective dihyrostilbene. The highest inhibition of germination of S. bicolor seeds were exhibited by the dihyrostilbenes especially dihyropinosylvin and its methylated derivative. Keywords: Stilbene, bibenzylalcohol, dihyrobibenzyl, Artemia salina, Sorghum bicolor, toxicity [Nig. J. Nat. Prod. And Med. Vol.6 2002: 19-25

Mycelial Growth and Antibacterial Metabolite Production by Wild Mushrooms

Russula sp. and Pycnoporus cinnabarinus   (wild mushrooms) were subjected to laboratory cultivation by spore germination and tissue culturing on Sabouraud dextrose agar plates. Subsequently, the growth and production of metabolite(s) were monitored in submerged fermentation for 7days using agar diffusion method. The result obtained showed that metabolite production peaked on the fourth day in Russula sp. and on the fifth day in Pycnoporus cinnabarinus with subsequent decrease in activity of the fermentation extract. Dry weight increases with fermentation time in both mushrooms

Bioautographic Evaluation of Antibacterial Metabolite Production by Wild Mushrooms

Russula sp. and Pycnoporus cinnabarinus   were subjected to liquid and solid state fermentation for metabolite production. Local rice substrate was used for the solid state fermentation to provide a cheap and readily available medium for laboratory cultivation of wild mushroom. Bioautography, a technique that combines chromatography with bioassay in situ allows the localization of the active constituent. The result showed that in submerged fermentation, both the culture filterate and mycelial extract of Russula sp. displayed antimicrobial activity while only the culture filtrate demonstrated activity in Pycnoporus cinnabarinus.. The activity of the solid state fermentation was exhibited by the ethyl acetate fractions while the aqueous fraction showed no activity. The comparison of the culture filtrates (ethyl acetate fractions) of submerged fermentation and the ethyl acetate fractions of solid state fermentation displayed similar activities

Biflavonoids of Calophyllum venulosum

10.1021/np970303fJournal of Natural Products60121245-1250JNPR

Replication of HIV-1_NL4-3, HIV-1_Δvpu, and drug-resistant HIV-1 strains in CEM-GXR cells.

<p>Data shown are at Day 4 in the presence of 0.1 μM of established ARVs, relative to the replication rate of each HIV-1 strain in the presence of 0.1% DMSO vehicle control. *, p < 0.004 vs. HIV-1_NL4-3 replication.</p

Effects of compounds on HCV replication.

<p><b>A,</b> Cell viability at 72 h post-infection in the presence of compounds at defined concentrations. Data are normalized to the percent of viable cells in a HCV-infected culture plus 0.1% DMSO. <b>B,</b> HCV replication at 72 h post-infection in the presence of compounds. Data are normalized to percent HCV-infected cells plus 0.1% DMSO.</p