Computational and Experimental Insights into Isocryptolepine Derivatives as Potential Antimalarial

Abstract

Malaria continues to constitute an imminent threat to the globe's health, particularly among those that are more vulnerable in locations with little resources. Plasmodium falciparum, the most lethal malaria parasite, has developed resistance to current antimalarial interventions, prompting an ongoing search for new therapeutic agents. The current research investigates the possibility of isocryptolepine derivatives as inhibitors of P. falciparum (PfDHFR), a key enzyme in the parasite's pyrimidine biosynthesis pathway. The research incorporates molecular docking and pharmacokinetic studies of 235 isocryptolepine derivatives, with an emphasis on their biological activity as antimalarial drugs. Our investigation focuses on the synthesis of innovative antimalarial drugs by molecular docking and in-silico ADMET investigations. Molecular docking investigation succors to recognized significant adhesion, aiding the delineation of enhanced medicinal products; the docking score of the created chemical varies from -8.66487 to -5.5531 Kcal/mol. Studies on in-silico pharmacokinetics indicate that certain substances have promising therapeutic potential, which is endorsed by appropriate molecular weight and oral absorption values in humans it assist in the development of innovative isocryptolepine derivatives with enhanced antimalarial activity, which is guided by these discoveries. To develop newer isocryptolepine derivatives with enhanced antimalarial activity, the compounds that were generated were analyzed using various spectrum analysis techniques.