{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:03:12Z","timestamp":1791925392894,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T00:00:00Z","timestamp":1404950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A number of novel spiro-pyrrolidines\/pyrrolizines derivatives were  synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2a\u2013n. Azomethine ylides were generated  in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 \u03bcM) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-\u03b1-Phenyl substituted spiro-pyrrolidine derivatives (5a\u2013n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a\u2013n, a number of derivatives including 6a\u2013c and 6i\u2013m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines\/pyrrolizines.<\/jats:p>","DOI":"10.3390\/molecules190710033","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T11:22:59Z","timestamp":1404991379000},"page":"10033-10055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Facile, Regio- and Diastereoselective Synthesis of  Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities"],"prefix":"10.3390","volume":"19","author":[{"given":"Abdulrahman","family":"Almansour","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P.O.Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P.O.Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzana","family":"Beevi","sequence":"additional","affiliation":[{"name":"New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan-301030, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Shirazi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"},{"name":"School of Pharmacy, Chapman University, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnah","family":"Osman","sequence":"additional","affiliation":[{"name":"School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rusli","family":"Ismail","sequence":"additional","affiliation":[{"name":"Centre of Excellence for Research in AIDS, University Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Choon","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellen","family":"McCaffrey","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Nahhas","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8600-0893","authenticated-orcid":false,"given":"Keykavous","family":"Parang","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA"},{"name":"School of Pharmacy, Chapman University, Irvine, CA 92618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan-301030, India"},{"name":"Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1002\/1521-3773(20000915)39:18<3168::AID-ANIE3168>3.0.CO;2-U","article-title":"Multicomponent reactions with isocyanides","volume":"39","author":"Domling","year":"2000","journal-title":"Angew. 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