Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities

Almansour, Abdulrahman I. and Kumar, Raju Suresh and Beevi, Farzana and Shirazi, Amir Nasrolahi and Osman, Hasnah and Ismail, Rusli and Tan, Soo Choon and Brian, Sullivan and Kellen, McCaffrey and Nahhas, Alaa and Parang, Keykavous and Ali, Mohamed Ashraf (2014) Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities. Molecules, 19 (7). pp. 10033-10055. ISSN 1420-3049

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Abstract

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–n. 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 μM) 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-α-Phenyl substituted spiro-pyrrolidine derivatives (5a–n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a–n, a number of derivatives including 6a–c and 6i–m 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 μM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.

Item Type:	Article
Subjects:	Q Science > QD Chemistry > QD1-999 Chemistry R Medicine > R Medicine (General) > R735-854 Medical education. Medical schools. Research
Divisions:	Institut Penyelidikan Perubatan Molekul (Institute for Research in Molecular Medicine INFORMM) > Article Pusat Pengajian Sains Kimia (School of Chemistry) > Article
Depositing User:	Mr Noorazilan Noordin
Date Deposited:	22 Feb 2018 00:54
Last Modified:	22 Feb 2018 00:55
URI:	http://eprints.usm.my/id/eprint/39099

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