Design and synthesis of novel tetrazolo quinoline bridged isatin derivatives as potential anticancer leads against MIA PaCa-2 human pancreatic cancer cell line

Human pancreatic carcinoma is known for its aggressiveness, low survival rate, and attractive target for anticancer evaluation. To target pancreatic cancer, new anticancer scaffolds are necessary. Hence, biodynamically potent tetrazole fused quinoline bridged isatin molecules (TQI) were considered for design and further synthesized. As a preliminary step, in silico pharmacokinetic properties were screened, followed by molecular docking against cyclooxygenase-2 (PDB ID: 1CX2). The TQI (1-8) molecules were found to be drugable, in silico and docking results of compounds TQI1, TQI2, TQI6, and TQI7 were found to have higher binding affinity (-9.5 to-10.8 kcal/mol) and also greater interaction with the active site; HIS207 residue of COX-2. As a result of the influx of in silico evaluation, synthesis was carried out and characterized by spectroscopic techniques like FTIR, LCMS and NMR. The in vitro cytotoxicity study of TQI1, TQI2, TQI6, and TQI7 molecules shows a 60.17 +/- 3.12 mu M, 74.49 +/- 3.45 mu M, 93.63 +/- 4.10 mu M, and 93.63 +/- 4.10 mu M IC50 against the MIA PaCa-2 cancer cell line. The results suggest that they can be considered as potential leads for next level evaluation. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study designed and synthesized novel tetrazole fused quinoline bridged isatin molecules with biodynamic activity, which showed higher cytotoxicity against pancreatic cancer cell lines in vitro and suggested potential for further evaluation.