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

• Published in: Journal of molecular structure 2023-04, Vol.1277, p.134772, Article 134772
• Main Authors: Patil, Pradeep, B． N．, Nippu, Satyanarayan, N． D．, Pore, Santosh, Zond, Rutuja, Gurav, Akshay, Hangirgekar, Shankar, Sankpal, Sandeep
• Format: Article
• Language: English
• Subjects: ADMET; COX-2; Docking; Ionic liquid; Pancreatic cancer
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134772

•Synthesis of novel spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] derivatives using [MerTEA][FeCl4] catalyst in aqueous media.•In vitro cytotoxicity assay of synthesized compounds on Min-6 cells.•Greater interaction and affinity of spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] with protein observed in docking study.•Evaluation of drug-likeness study and ‘In silico’ ADMET prediction. 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. A series of novel spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] derivatives were synthesized by one-pot four-component reaction of ethyl acetoacetate, hydrazine hydrate, malononitrile and various substituted isatins catalyzed by polymer supported ionic liquid (PSIL) in H2O at ambient temperature condition. Newly synthesized compounds were fully characterized by FT-IR, 1H and 13C NMR and mass spectrometry. Significant advantages of current protocol like easy scale up, reusable catalyst, superior green credentials, mild conditions, excellent yields and no chromatographic separation make them superior than existing methods. The in vitro cytotoxicity studies appreciated the considerable potency of synthesized compounds against pancreatic beta-cell line (Min-6) followed by molecular docking studies, drug-likeness and ADMET evaluation. [Display omitted]