Now-a-days, entire Pharmaceutical Industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of New Chemical Entities (NCEs). Hence, the challenge is to select most druggable targets and to search the equivalent drug-like compounds, which also possess specific Pharmacokinetic & Toxicological properties that allow them to be developed as drugs.
The present research work includes the studies of developing new Anticancer heterocycles by using molecular modeling technique. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of literature survey and considering the need to develop newer Anticancer agents, new Phenazinamine derivatives were designed by subjecting the nucleus to molecular modelling viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then, in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its Anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess log P and drug likeness values comparable with the standard Imatinib (used for Anticancer activity studies) and also with the standard drug methotrexate (used for Antimitotic activity studies).
Keywords: Phenazinamine, GQSAR, Docking, Anticancer
Abbreviations: GQSAR- Group based quantitative structural relationship, PASS- - Prediction of Activity Spectra for Substances