Title

Molecular docking, synthesis and biological evaluation of ergosterylferulate as a HMG-CoA reductase inhibitor.

Authors

Aziz, Syaikhul; Elfahmi; Soemardji, Andreanus A.; Sukrasno

Abstract

In the present study, ergosteryl-ferulate (5), oryzanol analog was evaluated for its possibility as the inhibitor of HMG-CoA reductase (HMGR), through in silico and in vitro approach. Firstly, the study was conducted through molecular docking simulation using AutoDock Tools software to predict the interaction of 5 in complexes with HMGR. In addition, four major compounds of oryzanol (1-4) were employed as a comparison. Secondly, 5 was synthesized through esterification using thionyl chloride as an activator. Lastly, 5 was evaluated for its capacity to inhibit HMGR activity using HMGR assay kit. Molecular docking simulation results suggest that oryzanol (1-4) and 5 exhibited a binding affinity against HMGR. The activity of 5 was predicted to be the best among the oryzanol compounds (1-4), in which, the free binding energy and inhibition constant were -4.17 kcal/mol and 0.88mM. The in vitro assay showed that 5 had inhibitory activity against HMGR 1.93 times higher than oryzanol. In summary, 5 has more potential candidates for HMGR inhibitor than oryzanol.

Subjects

MOLECULAR docking; REDUCTASE inhibitors; BIOSYNTHESIS; THIONYL chloride; BINDING energy; SOFTWARE development tools

Publication

Pakistan Journal of Pharmaceutical Sciences, 2020, Vol 33, Issue 3, p997

ISSN

1011-601X

Publication type

Academic Journal

DOI

10.36721/PJPS.2020.33.3.REG.997-1003.1