3D-QSAR and insilico study: Modeling parameters for designing new selective 12-LO enzymes inhibitors

Abstract

Selective 5-LO and 12-LO enzyme inhibitors have attracted much attention in recent times in the design of novel anthracenone derivatives, which may be used in cancer and psoriasis. However, not much computational studies has been done to examine specific type of parameters beneficial for anthracenone derivatives against 12-LO inhibitions. In our preliminary study we have done 2D QSAR studies by include a series of 2-arylalkyl substituted anthracenone derivatives having inhibitory action on 12-LO isoforms in epidermal homogenate of mice, bovine platelets and porcine leukocyte. These studies produced good predictive models and give statistically significant correlations with selective 12-LO enzyme inhibition. So these structural activity relationship studies were extended to 3DQSAR model studies utilizing theoretical molecular descriptors that can be calculated directly from molecular structures. All the descriptors were selected by genetic algorithm and multiple linear regression (MLRA) methods. All the QSAR models were validated by leave one out (LOO) method. In addition, insilico toxicity studies were also done. These all studies helps in designing some novel anthracenone derivatives with selective 12-LO enzyme inhibition activity with less toxicity.