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Inhibition of Plasmodium falciparum Fatty Acid Biosynthesis (FAS-II Pathway) by Natural Flavonoids: A Computer-Aided Drug Designing Approach

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Abstract

Malaria is a fever sickness caused by Plasmodium parasites that are transmitted to humans by mosquito bites from infected female Anopheles mosquitos. Intracellular malaria parasites require lipids for the growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. Considering widening resistance of resistant Plasmodium parasites and thus, failing conventional antimalarial agents, we herein analyzed a set of 109 flavonoids in four protein structures including three homology models and one experimentally obtained crystal structure were conducted to obtain the probable conformations of ligands and their binding affinities. Our results suggested Volkensiflavone, Bilobetin and Sciadopitysin as lead candidates for further detailed analysis and testing their synthetic analogues for their in-vitro anti-malarial potentials.

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Acknowledgements

Authors of this article are thankful to Dept. Of Pharmaceutical Sciences, Birla Institute of Technology, Mesra for their facility and academic support. SM also wish to thank the BIT, Mesra for the provision of IRF for year 2022, session SP.22.

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  1. Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Jharkhand, 835215, India

    Anima Pandey, Sagar S. Shyamal, Raunak Shrivastava, Sparsh Ekka & Suraj N. Mali

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  1. Anima Pandey
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Pandey, A., Shyamal, S.S., Shrivastava, R. et al. Inhibition of Plasmodium falciparum Fatty Acid Biosynthesis (FAS-II Pathway) by Natural Flavonoids: A Computer-Aided Drug Designing Approach. Chemistry Africa 5, 1469–1491 (2022). https://doi.org/10.1007/s42250-022-00449-7

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