QSAR Study of Asiatic Acid and its Derivatives as Potential Inducible Nitric Oxide Synthase (INOS) InhibitorsAuthor(s): Ida Musfiroh, W. Sri Rizky, Winasih, Ahmad Muhtadi, Rahmana E. Kartasasmita and Slamet Ibrahim
Asiatic acid is a pentacyclic triterpenoid bioactive compound isolated from pegagan (Centella asiatica), which has been reported to show anti-inflammatory activities by inhibition of NO production. The aims of this study were to obtain model of Quantitative structure activity relationship (QSAR) of some triterpenoids suitable for prediction of asiatic acid and its derivatives as potential inhibitor of inducible nitric oxide synthase (iNOS). The method includes optimization of molecular geometry with semi-empirical method AM1 using hyperchem 8.01, selection and calculation of suitable descriptors using molecular operating environment (MOE 2009.10) and generating and validating of QSAR models. The QSAR models and their validation were performed by statistical application prrogram. The results revealed that the most suitable QSAR model is Log 1/C50 = -0.798 (± 0,207) AM1_HOMO + 0.515 (± 0.185) Log P – 0.937 (± 0.131) apol + 0.053 (± 0.015) vdw_area + 3.264 (± 0.678) mr – 1.299 (± 4.135) with r = 0.845, F = 16.451 and n = 43. The modified of hydroxy group, carboxylic group and rearrangemet of double bond of asiatic acid structures have more higher iNOS inhibitory activities than those of asiatic acid.