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 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro- pyrrolidines/pyrrolizines.
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Authors | Abdulrahman I Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Choon, Brian Sullivan, Kellen McCaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 19
Issue 7
Pg. 10033-55
(Jul 10 2014)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 25014532
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Pyrrolidines
- Spiro Compounds
- pyrrolidine
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Topics |
- Antineoplastic Agents
(chemical synthesis, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Chemistry Techniques, Synthetic
- Humans
- Pyrrolidines
(chemical synthesis, pharmacology)
- Spiro Compounds
(chemical synthesis, pharmacology)
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