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

Authors

Abdulrahman I. Almansour, King Saud University
Raju Suresh Kumar, King Saud University
Farzana Beevi, Sunrise University
Amir Nasrolahi Shirazi, Chapman UniversityFollow
Hasnah Osman, Universiti Sains Malaysia
Rusli Ismail, University of Malaya
Tan Soo Chen, Universiti Sains Malaysia
Brian Sullivan, University of Rhode Island
Kellen McCaffrey, University of Rhode Island
Alaa Nahhas, University of Rhode Island
Keykavous Parang, Chapman UniversityFollow
Mohamed Ashraf Ali, Sunrise University

Document Type

Article

Publication Date

2014

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 M) 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-alpha-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 mu M in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.

Comments

This article was originally published in Moleculues, volume 19, issue 7, in 2014. DOI: 10.3390/molecules190710033

Recommended Citation

Almansour, Abdulrahman I., Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Choon et al. "Facile, Regio-and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities." Molecules 19.7 (2014): 10033-10055.
DOI:10.3390/molecules190710033

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This work is licensed under a Creative Commons Attribution 3.0 License.