Background: Cancer is the leading cause of death worldwide. Induction of apoptosis in
cancer cell is the main strategy for the development of anticancer agents targeting apoptosis pathway.
Procaspase-3 is one such target for the induction of apoptosis via activation of caspase 3. Novel
molecules are needed as procaspase-3 activators which will induce apoptosis in cancer cell.
Objective: The main objective of this work is to design 2-substituted benzimidazole derivatives using
3D QSAR study, and to predict the activity of designed compounds as procaspase-3 activators, and
Method: 3D QSAR study was performed on the series of substituted benzothiazole derivatives using
Sybyl X software. Distill alignment was used for 3D QSAR analysis. Best CoMFA and CoMSIA
models were used for the activity prediction of designed compounds. External validation using
MAE-based criteria were performed, and applicability domain of QSAR models were also determined.
Osiris property explorer and Med Chem Designer software were used for the prediction of in
silico pharmacokinetic properties, and toxicities.
Results: CoMFA and CoMSIA models were developed using Distill alignment method, which were
statistically very good, and validated using well known procedures. Contour maps generated using
3D QSAR study were used for the design of novel compounds. Designed compound showed better
predicted activity, and no toxicity.
Conclusion: The present QSAR approach with predicted activity and physicochemical properties
helped in the design of benzimidazole derivatives as procaspase-3 activators and apoptosis inducer.