<p>Indole: The After Next Scaffold of Antiplasmodial Agents?</p>

Abstract

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.

Gut Microbiota-Derived Indole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima

“…Other indole compounds are antiplasmodial agents. For example, aminoindole ( 43 ), bisindole ( 44 ), piperidine indole ( 45 ), or spiroindolone ( 46 ) are known as scaffolds in the novel chemical classes of antiplasmodial agents exhibiting various modes of action, of which, aiming at the formation of hemozoin in Plasmodium falciparum , PfATP4 and melatonin receptor are the most commonly recognized modes of actions ( 47 ). Therefore, we evaluated whether ICOOH has any direct effect on sporozoite of E. maxima .…”

Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications

“…Indole-containing scaffolds represent an important class of bioactive natural products, − drugs, − and functional materials. , The Wen group has reported the first example of palladium-catalyzed assembly of benzocarbazoles 52 from simple indoles and cyclic diaryliodoniums 50 via dual C–H activation of indoles at positions C2 and C3 (Scheme A) . However, the double annulation at positions N1 and C2 products of indoles cannot be obtained with this protocol.…”

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis

“…Several good reviews have been published in recent years that are focused on indole derivatives, mainly natural products, with antimalarial activity [ 58 , 59 , 60 , 61 , 62 ]. For this reason, in this section, we only focus on the most relevant indole synthetic derivatives reported in the last decade.…”

“…Most indole-based compounds with antiplasmodial activity are natural-based compounds (e.g., indole alkaloid cryptolepine) and exert their activity against chloroquine-resistant Plasmodium strains by an unknown mechanism of action or by inhibiting hemozoin formation [ 59 , 60 ]. An exception is the spiroindolone NITD609; reported in 2010, it is the first molecule with a novel mechanism of action to successfully complete phase II studies for malaria in the last 25 years [ 76 ].…”