35 research outputs found
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
REVIEW Open Access
The potential of anti-malarial compounds derived from African medicinal plants. Part I: A pharmacological evaluation of alkaloids and terpenoids Amoa Onguéné et al
Molecular Modeling of Potential Anticancer Agents from African Medicinal Plants
Naturally occurring anticancer compounds
represent about half of
the chemotherapeutic drugs which have been put in the market against
cancer until date. Computer-based or <i>in silico</i> virtual
screening methods are often used in lead/hit discovery protocols.
In this study, the âdrug-likenessâ of âŒ400 compounds
from African medicinal plants that have shown <i>in vitro</i> and/or <i>in vivo</i> anticancer, cytotoxic, and antiproliferative
activities has been explored. To verify potential binding to anticancer
drug targets, the interactions between the compounds and 14 selected
targets have been analyzed by <i>in silico</i> modeling.
Docking and binding affinity calculations were carried out, in comparison
with known anticancer agents comprising âŒ1â500 published
naturally occurring plant-based compounds from around the world. The
results reveal that African medicinal plants could represent a good
starting point for the discovery of anticancer drugs. The small data
set generated (named AfroCancer) has been made available for research
groups working on virtual screening
Distibution curves for some computed ADME parameters.
<p>(A) logB/B, (B) log<i>K</i><sub>HSA</sub>, (C) logHERG. For subfigure B, the <i>x</i>-axis label is the lower limit of binned data, e.g. â2 is equivalent to â2 to â1. The colour codes are according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078085#pone-0078085-g005" target="_blank">Figure 5</a>.</p
Summary of average predicted pharmacokinetic property distributions of the total AfroDb library in comparison with the various subsets.
<p>Summary of average predicted pharmacokinetic property distributions of the total AfroDb library in comparison with the various subsets.</p
2D structures of the three compounds with log <i>P</i> values >14, included in AfroDb.
<p>2D structures of the three compounds with log <i>P</i> values >14, included in AfroDb.</p
Pairwise comparison of mutual relationships between molecular descriptors.
<p>(A) The distribution of the calculated log <i>P</i> versus MW, (B) HBA against MW, (C) HBD against MW and (D) NRB versus MW. LCR represents the Lipinski compliant regions.</p
2D structures of selected promising compounds derived from the African flora and included in AfroDb.
<p>2D structures of selected promising compounds derived from the African flora and included in AfroDb.</p
Virtualizing the p-ANAPL Library: A Step towards Drug Discovery from African Medicinal Plants
<div><p>Background</p><p>Natural products play a key role in drug discovery programs, both serving as drugs and as templates for the synthesis of drugs, even though the quantities and availabilities of samples for screening are often limitted.</p><p>Experimental approach</p><p>A current collection of physical samples of > 500 compound derived from African medicinal plants aimed at screening for drug discovery has been made by donations from several researchers from across the continent to be directly available for drug discovery programs. A virtual library of 3D structures of compounds has been generated and Lipinskiâs âRule of Fiveâ has been used to evaluate likely oral availability of the samples.</p><p>Results</p><p>A majority of the compound samples are made of flavonoids and about two thirds (2/3) are compliant to the âRule of Fiveâ. The pharmacological profiles of thirty six (36) selected compounds in the collection have been discussed.</p><p>Conclusions and implications</p><p>The p-ANAPL library is the largest physical collection of natural products derived from African medicinal plants directly available for screening purposes. The virtual library is also available and could be employed in virtual screening campaigns.</p></div