Title:Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals
VOLUME: 19 ISSUE: 7
Author(s):Indira G. Shibi, Lilly Aswathy, Radhakrishnan S. Jisha, Vijay H. Masand and Jayant M. Gajbhiye
Affiliation:Department of Chemistry, Sree Narayana College, Chempazhanthy P.O. Box: 695587, Kerala, India.
Keywords:Malaria, Plasmodium falciparum, virtual screening, weka, ADME, molecular operating environment, molecular
docking.
Abstract:Malaria parasites show resistance to most of the antimalarial drugs
and hence developing antimalarials which can act on multitargets rather than a
single target will be a promising strategy of drug design. Here we report a new
approach by which virtual screening of 292 unique phytochemicals present in 72
traditionally important herbs is used for finding out inhibitors of plasmepsin-2
and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings
of the selected molecules by Random Forest algorithm model of Weka using the
bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292
phytochemicals to be active against the targets. Toxtree scan cautioned 21
compounds to be either carcinogenic or mutagenic and were thus removed for
further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as
per the ‘rule of five’ criteria. Out of ten antimalarial drug targets, only two target proteins such as
3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The
potential binding of the selected 46 compounds to the active sites of these four targets was
analyzed using MOE software. The docked conformations and the interactions with the binding
pocket residues of the target proteins were understood by ‘Ligplot’ analysis. It has been found that
8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies.
Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone
(Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking
score.
