In silico evaluation of 6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8 H )-one compounds: an insight into design of less toxic anticancer drugs

The study presents both three-dimensional quantitative structure–activity relationship (3D-QSAR) and quantitative/qualitative structure–toxicity relationship (QSTR) analyses for the 6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8 H )-one compounds that are known to have activity against a variety of cancers including colon, lung, head and neck carcinoma. The study was based on models developed from computed molecular and toxicity descriptors obtained solely from the structure of the compounds. The 3D-QSAR analysis suggests specific role of steric, electrostatic and hydrophobic fields of the compounds for anticancer activity as derived by mathematical equations. Although the study discusses a few important relevant 3D-QSAR results from our previously reported study, the focus here is to assess in silico evaluations of ADME/toxicity (QSTR) profiles of the 6-(2,6-dichlorophenyl)-pyrido[2,3-d]pyrimidin-7(8 H )-ones to design analogs of these compounds for development of anticancer therapeutics for early-stage treatments. Our calculated QSTR profiles predicted the potential for design of better derivatives by compromising high activity with less toxicity through chemical tweaking as a trade-off.