Structure activity relationship in β-carboline derived anti-malarial agents

Malaria, even though an avoidable and treatable disease, can be fatal if ignored. Artemisinin Combination Therapy (ACT) and RTS, S/AS01 vaccine (Mosquirix (TM)) are the only modest means available with humans to overcome malaria, a lethal affliction wreaking havoc across the globe. Employment of ACT is associated with problems such as 'Artemisinin Resistance' and the 'Hypnozoite conundrum' that hinder the complete eradication of malaria. In this view, the natural products specifically comprising beta-carboline scaffold have shown good antiplasmodial responses against different strains of malaria. Taking these observations forward, researchers have performed structure-activity relationship (SAR) studies around three different beta-carboline skeletons (tetrahydro beta-carbolines, dihydro beta-carbolines, beta-carbolines) to design new beta-carboline derived heterocyclic structures or modified naturally occurring derivatives. In addition, different approaches such as dimerization and linkage to other moieties have also been adopted to enhance the antimalarial activity. The present review describes a comprehensive SAR study encapsulating various natural and synthetic beta-carbolines to elaborate upon the utility of these skeletons in designing drugs to subdue this deadly disease. (C) 2021 Published by Elsevier Masson SAS.