MOLECULAR DOCKING AND ADMET STUDY OF NOVEL BENZO[B]XANTHONE DERIVATIVES AS A PF-FALCIPAIN 2 INHIBITOR

Abstrak

The emergence of P.falciparum strains that are resistant to chloroquine (CQ), sulfadoxine–pyrimethamine (SP), and, more recently, artemisinin combinations (ACT), necessitates the development of novel antimalarial agents, including secondary metabolites. Xanthone is a tricyclic secondary metabolite,  in the form of a yellowish solid isolate, whose structure  offers a number of biological activities. One of them as an antimalarial agent. An antimalarial activity can be predicted through in-silico tests, that serve as a preliminary approach before conducting in vitro or in vivo tests. This study presents the first computational investigation of novel benzo[b]xanthone targeting falcipain 2, a key protein that synthesises essential amino acids in falciparum.  The methods used were molecular docking with the Autodockvina protocol and ADMET web-based analysis on the PKCSM website. 4-chlorobenzo[b]xanthone emerged as the lead candidate, exhibiting superior binding affinity of -7.64 kcal/mole and a favorable ADMET values as drugs candidate. The 4-chlorobenzo[b]xanthone show promising activity, provides a foundation for developing next-generation antimalarials against resistant P. falciparum strains.