Green synthesis and anticancer evaluation of dispiroheterocycles containing isatin, tetrahydrobetacarboline, pyrrolidine and aurone motifs

• Published in: Journal of molecular structure Vol. 1321; p. 139870
• Main Authors: Mohan, Maneesh, Gilbert, Ginson, Sandhya, K.S., Nair, Arsha S, Vishwakarma, Arti, Deepthi, Ani
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-02-2025
• Subjects: Anticancer; Aurone; Azomethine ylide; Dispiroheterocycle; Thioaurone; Dispiroheterocycle; Aurone; Thioaurone; Anticancer; Azomethine ylide
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139870

•Green stereoselective synthesis of dispiro heterocycles from tetrahydro-β-carboline derived azomethine ylide (AY) is described.•Dispiro heterocycles were formed in excellent yield and were isolated by chromatography-free method and characterized by spectroscopic techniques and SCXRD.•Structural optimization and frequency calculations for conformation was done by DFT calculations using B3LYP/6-31G(d,p) level of theory.•All the derivatives were tested in silico by using Auto Dock and compound 4e exhibited strongest binding with PLK1 (-8.71 kcal/mol).•In vitro studies by MTT assay showed that the compound 4e exhibited cell viability less than 20 % with an effective dose of 6.25μg/mL and LC 50 of 4.68 μg/mL.
Twenty-one dispiropyrrolidine derivatives were synthesized using a green protocol by the classical [3+2] cycloaddition reaction of aurones with azomethine ylide derived from 1,2,3,4-tetrahydro-β-carboline and isatin. All compounds were well-characterized and out of the twenty-one derivatives, compound 4e, was found to exhibit strongest binding affinity of 8.71 kcal/mol and good stability with PLK1 protein target, which was predicted by molecular docking and molecular dynamic simulation. In vitro studies indicated that the compound exhibited low LC50 value of 4.68 μg/mL on the MCF-7 breast cancer cell lines using MTT assay.
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