Green Synthesis of Spiro Compounds with Potential Anticancer Activity through Knoevenagel/Michael/Cyclization Multicomponent Domino Reactions Organocatalyzed by Ionic Liquid and Microwave-Assisted

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Westphal, Regina ; Venturini Filho, Eclair ; Loureiro, Laiza Bruzadelle ; Tormena, Claudio Francisco ; Pessoa, Claudia ; Guimaraes, Celina de Jesus ; Manso, Mariana Palmeira ; Fiorot, Rodolfo Goetze ; Campos, Vinicius Rangel ; Lamounier Camargos Resende, Jackson Antonio ; Medici, Fabrizio ; Greco, Sandro Jose

• Document type: Journal article
• Source: Molecules; v. 27, n. 22, p. 15-pg., 2022-11-01.

Abstract

In this work a microwave-assisted Knoevenagel/Michael/cyclization multicomponent domino methodology, using ethanol as solvent and the ionic liquid 1-methylimidazolium chloride as catalyst was developed for the synthesis of spiro compounds. The reaction conditions considered ideal were determined from a methodological study varying solvent, catalyst, amount of catalyst, temperature, and heating mode. Finally, the generality of the methodology was evaluated by exploring the scope of the reaction, varying the starting materials (isatin, malononitrile, and barbituric acid). Overall, the twelve spiro compounds were synthesized in good yields (43-98%) and the X-ray structure of compound 1b was obtained. In addition, the in vitro antiproliferative activities of the spirocycles against four types of human cancer cell lines including HCT116 (human colon carcinoma), PC3 (prostate carcinoma), HL60 (promyelocytic leukemia), and SNB19 (astrocytoma) were screened by MTT-based assay. It is noteworthy that spiro compound 1c inhibited the four cell lines tested with the lowest IC50 values: 52.81 mu M for HCT116, 74.40 mu M for PC3, 101 mu M for SNB19, and 49.72 mu M for HL60. (AU)

• FAPESP's process: 20/10246-0 - Nuclear magnetic resonance spectroscopy: from pulse sequences to structural assignments
• Grantee: Claudio Francisco Tormena
• Support Opportunities: Research Projects - Thematic Grants