Drug Design, Development and Therapy (Nov 2020)
Indole: The After Next Scaffold of Antiplasmodial Agents?
Abstract
Abdrrahman Shemsu Surur,1 Solomon Assefa Huluka,2 Melese Legesse Mitku,3 Kaleab Asres4 1CDT-Africa, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Pharmacology and Clinical Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia; 3Department of Pharmaceutical Chemistry, University of Gondar, Gondar, Ethiopia; 4Department of Pharmaceutical Chemistry and Pharmacognosy, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Abdrrahman Shemsu SururCDT-Africa, Addis Ababa University, P. O Box 182932, Addis Ababa, EthiopiaTel +251-911171194Email [email protected]: Malaria remains a global public health problem due to the uphill fight against the causative Plasmodium parasites that are relentless in developing resistance. Indole-based antiplasmodial compounds are endowed with multiple modes of action, of which inhibition of hemozoin formation is the major mechanism of action reported for compounds such as cryptolepine, flinderoles, and isosungucine. Indole-based compounds exert their potent activity against chloroquine-resistant Plasmodium strains by inhibiting hemozoin formation in a mode of action different from that of chloroquine or through a novel mechanism of action. For example, dysregulating the sodium and osmotic homeostasis of Plasmodium through inhibition of PfATP4 is the novel mechanism of cipargamin. The potential of developing multi-targeted compounds through molecular hybridization ensures the existence of indole-based compounds in the antimalarial pipeline.Keywords: indole, antimalarial agents, hemozoin inhibition, PfATP4, multi-target approach
