ISSN : 0970 - 020X, ONLINE ISSN : 2231-5039
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Abstract

Xanthone as Antimalarial: QSAR Analysis, Synthesis, Molecular Docking and In-vitro Antimalarial Evaluation

Jufrizal Syahri1,2, Emmy Yuanita2,3, Beta Achromi Nurohmah2, Muhammad Hizbul Wathon4, Rahmadini Syafri1,Ria Armunantoand Bambang Purwono2

DOI : http://dx.doi.org/10.13005/ojc/330104


Abstract:

The rational design of eighteen new antimalarial compounds from xanthone derivatives has been conducted based on Quantitative Structure-Activity Relationship(QSAR) calculation using semi-empirical AM1 methods. The best equation model obtained from QSAR calculation was Log pIC50 = 2.997 - 29.256 (qO8) - 138.234 (qC9) - 6.882 (qC12) - 107.836 (qC14) + 48.764 (qO15). Among the designed compounds, 3,6-dihydroxy-9H-xanthen-9-one (26) and 3,4,6-trihydroxy-9H-xanthen-9-one (27) have been synthesized and investigated their in-vitro antimalarial activities against the chloroquine-sensitive 3D7 strain. An in-vitro antimalarial activity of compound 26 and 27 showed to be highly potential as antimalarial compounds with IC50 of 0.71 and 0.11 µM respectively. Molecular docking studies of compound 26 and 27 showed the formation of a binding interaction between the compounds with the amino acids Ala16, Ser108, Phe58, Asp54 and Leu46, which is the crucial amino acids for antimalarial activity based on the protein-ligand co-crystal structure of  WR99210(1,3,5-triazine, a pre-clinical molecule as P. falciparum DHFR-TS inhibitor).

Keywords:

Antimalarial; Docking; Semi-empirical AM 1; QSAR; Xanthone

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