This study was designed to assess the cytotoxicity, anti-HIV and antibacterial efficacy of various solvent extracts of roots, stem and leaves of Alchornea laxiflora, as well as five compounds isolated from its methanolic stem extract viz.; ellagic acid (1); 3-O-methyl-ellagic acid (2), 3-O-beta-D-glucopyranosyl-beta-sitosterol (3), 3-O-acety-loleanolic acid (4) and 3-O-acetyl-ursolic acid (5). The tested crude extracts were prepared from several solvent polarities including: hexane (Hex), chloroform (CHCl3), ethyl acetate (EtOAc), ethanol (EtOH), methanol (MeOH) and water (H2O). The anti-HIV properties were assessed on HIV-1 subtype C integrase while the cytotoxicity was tested against Hela cells. The antibacterial activity was studied on a panel of pathogens including gastrointestinal, skin, respiratory and urinary-tract infection causing Gram positive bacteria viz.; Bacillus cereus (ATCC 11778), Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 25923) and Staphylococcus saprophyticus (ATCC 15305)] and Gram-negative bacteria, i.e., Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Moraxella catarrhalis (ATCC 23246). All the tested samples were determined to be non-toxic due to the low inhibitions observed. The most potent anti-HIV activity was observed for the methanolic extract of A. laxiflora root (ALR4) with an IC50 value of 0.21 ng/ml, which was more active than chicoric acid used as reference drug (6.82 nM). Roots, stem and leaves of A. laxiflora extracts exhibited antibacterial activities against most of the Gram-positive bacteria with the minimum inhibitory concentrations (MIC) ranging between 50 and 63 mu g/ml. Compounds 1-5 displayed antibacterial activities against S. saprophyticus with MIC values as low as 4 mu g/ml. The results inferred from this study demonstrate the potential of A. laxiflora root as a source for new anti-HIV drugs and scientifically validate the traditional use of A. laxiflora in the treatment of gastrointestinal, skin, respiratory and urinary tract related infections. These results reaffirm the ethnopharmacological significance of African traditional medicines. (C) 2018 SAAB. Published by Elsevier B.V. All rights reserved.

There is increasing requirement for the development of new drug protocols against malaria, a fatal disease caused by the lethal parasite Plasmodium falciparum. Leucine aminopeptidase (Pf LAP) of Plasmodium falciparum, is being pursued as a promising target for the discovery of novel antimalarials. The effects of silver nanoparticles (AgNPs) against P. falciparum leucine amino-peptidase (Pf LAP) and the human homolog (HsLAP) were compared. Pf LAP and HsLAP were expressed in Escherichia coli, and AgNPs (3-10 nm) characterized by ultra-violet spectroscopy and transmission electron microscopy. Pf LAP indicated a Km of 694 μM towards leucine-p-nitroanilide and a Vmax of 57.9 μmol.ml-1 · min-1 while HsLAP had a Km of 1.6 mM and Vmax of 119.6 μmol · ml-1 · min-1. On interaction with AgNPs (670 nM) Pf LAP was selectively inhibited (57.1%; Ki = 610 nM) relative to HsLAP (10.8%; Ki = 5.22 μM). Structural differences between the enzyme variants, particularly the orientation and distance of surface Met349 in Pf LAP and Met306 in HsLAP to the zinc binding sites were significant and may allow for selective targeting of Pf LAP by AgNPs. The viability of P. falciparum parasites was decreased when exposed to silver nanoparticles, with an IC50 value of 6.96 μM, compared to an IC50 value of 647.7 μM for human HeLa cells.