Classical QSAR Study on Chromene Derivatives as Lanosterol 14α -Demethylase Inhibitor: A Non Azole Antifungal Target

S.   G.   Kaskhedikar; M.   A.   Babu; M.      Lakshmi; P.      Vasanthanathan

doi:10.2174/157340606777724004

Abstract

A lanosterol 14α-demethylase inhibitors of chromene series were subjected to classical quantitative structural activity relationship studies. Apart from the indicator variables encoding for different group contribution, there are various physico-chemical descriptors like steric, thermodynamic and electronic parameters, which were applied to explore the structural requirements for inhibition of enzyme. Multiple linear regression analysis shows that substituents on the appended alkylated ether and the carbon chain length, which should not be more than six at R3 and R1 positions in the parent nucleus, are essential to modulate the activity. Electronic parameters such as highest occupied molecular orbital energy and dipole dipole energy have been found to play an important contribution for biological activity. From the orientation or distribution of the total molecular structures in 3D space, it was assessed that Principal Moments of Inertia at X-axis is detrimental for fungal inhibitory activity. Thus validated models bring important structural insights to aid the design of potent lanosterol 14α-demethylase inhibitors prior to their synthesis.

Keywords: austin model-1 calculation and anti mycotic agents, highest occupied molecular orbital, chromene derivative, cytochrome P450, QSAR

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