Comparative Shape and Electrostatic Study of Highly Potent and Selective CYP1B1 Inhibitor: Assessment of Active Site of CYP1B1 by Binding Mode Analysis Using Site Map Tool

Abstract:

Introduction: The major aim of drug design and discovery is to minimize the time and cost of drug discovery process. Various molecules which are promised to be potential candidate during computational and preclinical studies, shows the poor results during clinical trials due to less credibility of in silico results. This leads to increased burden of time and cost of drug discovery process. Methodology: A reliabel Shape and Electrostatic similarity based screening of ligands and assessment of druggability of the target protein provides a means to predict the negatives at an earlier stage of drug discovery pipeline. Two compounds (BNUA-3 & BNUB-13) reported from our lab were compared with ANF and TMS. Results and Discussion: Shape coefficient between BNUB-13 and TMS was 0.79 and electrostatic coefficient was 0.464 indicating that BNUB-13 is quite similar to TMS. Dscore values for ANF, TMS, BNUB-13 and BNAU-3 were also found to be similar, 1.404, 1.390, 1.389 and 1.366, respectively. Conclusion: The comparative studies of two highly potent CYP1B1 inhibitors revealed minimum structural information that can modulate the potency of the inhibitors. Meanwhile assessment of the active site of CYP1B1 has shown that CYP1B1 is a druggable target.

Key words: CYP1B1, Shape electrostatic coefficient, Sitemap analysis, Druggability, In silico ADME calculation.