Quantitative Structural Activity Relationship Studies for In Silico Prediction of In Vitro Cytotoxicity of NSAIDs in Colon Cancer Cell Lines

Non-steroidal anti-inflammatory drugs (NSAIDs) are evolving as the prototypical chemopreventive agents against colon cancer, an opinion nowadays reinforced by a substantial form of epidemiological, animal, and basic science data. Apart from their preventive role in the prophylaxis and management of colon cancer, NSAIDs at lower doses are widely employed in permutation with conventional anticancer drugs in order to reduce the dose related cytotoxic effects and to impart additive or synergistic therapeutic effect. In vitro cell-based cytotoxicity assays are effective techniques for hit ranking and lead optimization at the early stage of drug discovery. The present study has been focused on in silico screening and prediction of in vitro cytotoxicity (or growth inhibitory activity, GI50) of heterogeneous group of NSAIDs having flexibility in structure and cytotoxicity activity against DLD-1 and SW-480 colon cancer cell lines using 3DQSAR (3-dimensional quantitative structural activity relationship) SOMFA (self-organizing molecular field analysis) studies. Analysis of 3D-QSAR models through electrostatic and shape grids provide useful information about the steric, electrostatic potential contributions along with the combination of log P, total dipole moment and molar refractivity (MR) on GI50. The results obtained provided an insight on NSAIDs with optimum in vitro cytotoxicity activity and improved therapeutic profile.