Design, synthesis, docking studies and anticancer evaluation of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives on MIN-6 cancer cell line

Abstract

A series of spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] were synthesized by a one-pot four-component reaction of ethyl acetoacetate, hydrazine hydrate, malononitrile, and isatin catalyzed by new polymer-supported ionic liquid (PSIL) catalyst in an aqueous solution at ambient conditions. Newly synthesized compounds were fully characterized by FT-IR, 1H and 13C NMR, and mass spectrometry. The pharmacokinetic properties were screened and followed by molecular docking on COX-2 to check the in silico potency. Cytotoxicity of 5a-j molecules was evaluated against the Min-6 pancreatic cancer cell line. The 5a-j molecules have been found to have a good drugable profile and good binding affinity with the COX-2 enzyme. In addition, the in vitro cytotoxic potential of the synthesized compounds showed promising inhibition potential against cancer cell lines. The most promising compounds, 5e (IC50 11.33) and 5g (IC50 17.30) show the most remarkable cytotoxic activity as compared to other analogues. The results convey that the designed molecules are promising products for level-up biological evaluation.