In vitro screening identification and evaluation of diverse group of compounds for their anti plasmodial activity

Abstract

Malaria remains one of the serious infectious diseases causing widespread mortality newlineworldwide. Nearly half of the world population is at risk of contracting the disease, with newlinemajority of cases reported from Sub-Saharan African countries. The emergence of resistant newlineparasites against the available anti-malarial drugs, threatens to derail the malaria control and newlineelimination efforts and requires to keep the search for newer and effective drugs against the newlinemalaria parasite to go on. Keeping this challenge in mind, the goal of the present study was to newlinescreen and identify novel compounds belonging to different categories derived using different newlineapproaches, for anti-plasmodial activity. The first category of compounds were synthesized newlinebased on melatonin and indole based synthetic and natural anti-malarials. The screening of newlinethese compounds led to identification of an indole-based C2-arylimino tryptamine derivative newlinecompound (2j), that exhibited anti-plasmodial activity against both the wild-type and newlinechloroquine-resistant strains of the parasite. This compound specifically blocked the parasite newlinein trophozoite stage and was able to negate the effects of melatonin on parasite growth and newlinesynchrony. The second library of compounds were obtained from synthesis based on indole newlinebased derivatives (tetrahydro-and#946;-carbolines and spiropyrrolooxoindoles). Interestingly, the two newlinemost potent compounds of this library (compounds 2 and 3) exhibited similar lethality against newlineboth the wild-type and artemisinin-resistant strains of P. falciparum. Furthermore, the antiplasmodial effects of these compounds were mediated via enhanced ROS generation. The next newlinecategory of compounds that were tested in this study for anti-plasmodial activities, were newlineimidazolium based ionic liquids. 1-Decyl-3-methylimidazolium tetrafluoroborate newline([DMIM]BF4), identified from this category exhibited strong anti-plasmodial activity and newlineinhibited the parasite growth in a stage-specific manner and was also shown to perturb the host newlineRBC membrane.