{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:16:58Z","timestamp":1790957818247,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T00:00:00Z","timestamp":1668816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u201398%) 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 \u00b5M for HCT116, 74.40 \u00b5M for PC3, 101 \u00b5M for SNB19, and 49.72 \u00b5M for HL60.<\/jats:p>","DOI":"10.3390\/molecules27228051","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T04:33:32Z","timestamp":1669005212000},"page":"8051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Green Synthesis of Spiro Compounds with Potential Anticancer Activity through Knoevenagel\/Michael\/Cyclization Multicomponent Domino Reactions Organocatalyzed by Ionic Liquid and Microwave-Assisted"],"prefix":"10.3390","volume":"27","author":[{"given":"Regina","family":"Westphal","sequence":"first","affiliation":[{"name":"Chemistry Department, Federal University of Esp\u00edrito Santo, Fernando Ferrari Avenue 514, Vit\u00f3ria 29075-910, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eclair","family":"Venturini Filho","sequence":"additional","affiliation":[{"name":"Chemistry Department, Federal University of Esp\u00edrito Santo, Fernando Ferrari Avenue 514, Vit\u00f3ria 29075-910, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiza Bruzadelle","family":"Loureiro","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Campinas, Josu\u00e9 de Castro Street, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udio Francisco","family":"Tormena","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, University of Campinas, Josu\u00e9 de Castro Street, Campinas 13083-970, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Cear\u00e1, Fortaleza 60430-275, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5244-3522","authenticated-orcid":false,"given":"Celina de Jesus","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Cear\u00e1, Fortaleza 60430-275, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Palmeira","family":"Manso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Cear\u00e1, Fortaleza 60430-275, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo Goetze","family":"Fiorot","sequence":"additional","affiliation":[{"name":"Campus do Valonguinho, Institute of Chemistry, Fluminense Federal University, Niter\u00f3i 24020-141, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3676-5964","authenticated-orcid":false,"given":"Vinicius Rangel","family":"Campos","sequence":"additional","affiliation":[{"name":"Campus do Valonguinho, Institute of Chemistry, Fluminense Federal University, Niter\u00f3i 24020-141, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson Ant\u00f4nio Lamounier Camargos","family":"Resende","sequence":"additional","affiliation":[{"name":"Exact and Earth Sciences Institute, Federal University of Mato Grosso, Campus Universit\u00e1rio do Araguaia, Pontal do Araguaia 78698-000, MT, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1356-7244","authenticated-orcid":false,"given":"Fabrizio","family":"Medici","sequence":"additional","affiliation":[{"name":"Chemistry Department, University of Milan, Via Golgi 19, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-9295","authenticated-orcid":false,"given":"Sandro Jos\u00e9","family":"Greco","sequence":"additional","affiliation":[{"name":"Chemistry Department, Federal University of Esp\u00edrito Santo, Fernando Ferrari Avenue 514, Vit\u00f3ria 29075-910, ES, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/hlca.19390220179","article-title":"Etudes sur les mati\u00e8res v\u00e9g\u00e9tales volatiles X. 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