Cheminformatics and Computational Chemical Biology

Biography

Biography: Shalini Singh

Abstract

Coumarins such as [1], a natural product secluded from the Australian plant Leionema ellipticum, P. G. Wilson (Rutaceae), or the simple unsubstituted coumarin [2], were detected to act as effective inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1)[1−3]. Substituted coumarin such as sulfocoumarins (1,2-benzoxathiine 2,2-dioxides) possessing are the most important[4] class of Potent and Isoform-Selective Inhibitors of Tumor-Associated Carbonic Anhydrases CA IX[4]. I have attempted to build QSAR models using the OMEGA, MOPAC, PRECLAV, DRAGON and BROOD software to explore the correlations between the calculated molecular descriptors on the pool of 16 compounds and their experimental CAIX inhibitory activities. The quality of prediction is high enough (SE =0 .1680, r2=0 .9483; F 128.4198, Q= 8539). The virtual molecular fragment that lead to a significant increase of the inhibitor activity of hCA IX is C2HN3 , The virtual fragments , Br atom and NO2 leads to a significant decrease of the inhibitor activity value. The innovation of this work consists in not only exploring the structural attributes of bioactive molecules but in predicting in silico the structures of eleven new compounds which may show Tumor-Associated Carbonic Anhydrases IX (CAIX) inhibitory activity. The analogs of the lead molecule are generated by replacing selected fragments that have similar shape and electrostatics. The various pharmacokinetic evaluations and synthetic accessibility test were also carried out to search more suitable compounds. The molecules of the prediction set include many molecules having high computed activity.