In Vitro and In Silico Anti-plasmodial Evaluation of Newly Synthesized beta-Carboline Derivatives

摘要

Series of novel thiourea and guanidine conjugated beta-carbolines along with other analogues of this class were designed and synthesized for in vitro antimalarial activity against Plasmodium falciparum to overcome the threat of resistance to anti-malarial drug. Among them, two guanidine conjugated beta-carbolines 7a and 7c showed promising activities against both sensitive and resistant strains Pf3D7 and PfINDO with the IC50 values ranging from 0.6-1.0 mu M. The relative activities were further supported by in silico docking and binding studies of the synthesized scaffolds against specific targets, revealing that DHFR and FP3 may act as a potential target for 7a and 7c respectively.