Next Article in Journal
Polyphenolic Content, Antioxidant and Antimicrobial Activities of Lycium barbarum L. and Lycium chinense Mill. Leaves
Previous Article in Journal
Plumbagin Modulates Leukemia Cell Redox Status
Article Menu

Export Article

Open AccessArticle
Molecules 2014, 19(7), 10033-10055; doi:10.3390/molecules190710033

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

1
Department of Chemistry, College of Science, King Saud University, P.O.Box 2455, Riyadh 11451, Saudi Arabia
2
New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan-301030, India
3
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
4
School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
5
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
6
School of Pharmacy, Chapman University, Irvine, CA 92618, USA
7
Centre of Excellence for Research in AIDS, University Malaya, Kuala Lumpur 50603, Malaysia
*
Authors to whom correspondence should be addressed.
Received: 29 May 2014 / Revised: 24 June 2014 / Accepted: 1 July 2014 / Published: 10 July 2014
View Full-Text   |   Download PDF [594 KB, uploaded 10 July 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 2an. 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 (5an) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6an, a number of derivatives including 6ac and 6im 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. View Full-Text
Keywords: antiproliferative activity; diastereoselective synthesis; pyrrolizine; regio-selective synthesis; spiro-pyrolidine antiproliferative activity; diastereoselective synthesis; pyrrolizine; regio-selective synthesis; spiro-pyrolidine
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Almansour, A.I.; Kumar, R.S.; Beevi, F.; Shirazi, A.N.; Osman, H.; Ismail, R.; Choon, T.S.; Sullivan, B.; McCaffrey, K.; Nahhas, A.; Parang, K.; Ali, M.A. Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities. Molecules 2014, 19, 10033-10055.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top