Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI
2014
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| Subjects: | |
| Online Access: | http://eprints.usm.my/39099/1/Facile%2C_Regio-_and_Diastereoselective_Synthesis_of_Spiro-Pyrrolidine_and.pdf |
| _version_ | 1825833985558708224 |
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| author | Almansour, Abdulrahman I. Kumar, Raju Suresh Beevi, Farzana Shirazi, Amir Nasrolahi Osman, Hasnah Ismail, Rusli Tan, Soo Choon Brian, Sullivan Kellen, McCaffrey Nahhas, Alaa Parang, Keykavous Ali, Mohamed Ashraf |
| author_facet | Almansour, Abdulrahman I. Kumar, Raju Suresh Beevi, Farzana Shirazi, Amir Nasrolahi Osman, Hasnah Ismail, Rusli Tan, Soo Choon Brian, Sullivan Kellen, McCaffrey Nahhas, Alaa Parang, Keykavous Ali, Mohamed Ashraf |
| author_sort | Almansour, Abdulrahman I. |
| collection | USM |
| description | 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. |
| first_indexed | 2024-03-06T15:15:57Z |
| format | Article |
| id | usm.eprints-39099 |
| institution | Universiti Sains Malaysia |
| language | English |
| last_indexed | 2024-03-06T15:15:57Z |
| publishDate | 2014 |
| publisher | MDPI |
| record_format | dspace |
| spelling | usm.eprints-390992018-02-22T00:55:44Z http://eprints.usm.my/39099/ Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities Almansour, Abdulrahman I. Kumar, Raju Suresh Beevi, Farzana Shirazi, Amir Nasrolahi Osman, Hasnah Ismail, Rusli Tan, Soo Choon Brian, Sullivan Kellen, McCaffrey Nahhas, Alaa Parang, Keykavous Ali, Mohamed Ashraf QD1-999 Chemistry R735-854 Medical education. Medical schools. Research 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. MDPI 2014 Article PeerReviewed application/pdf en http://eprints.usm.my/39099/1/Facile%2C_Regio-_and_Diastereoselective_Synthesis_of_Spiro-Pyrrolidine_and.pdf 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 https://doi.org/10.3390/molecules190710033 |
| spellingShingle | QD1-999 Chemistry R735-854 Medical education. Medical schools. Research Almansour, Abdulrahman I. Kumar, Raju Suresh Beevi, Farzana Shirazi, Amir Nasrolahi Osman, Hasnah Ismail, Rusli Tan, Soo Choon Brian, Sullivan Kellen, McCaffrey Nahhas, Alaa Parang, Keykavous Ali, Mohamed Ashraf Facile, Regio- and Diastereoselective Synthesis of Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities |
| title | Facile, Regio- and Diastereoselective Synthesis of
Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities |
| title_full | Facile, Regio- and Diastereoselective Synthesis of
Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities |
| title_fullStr | Facile, Regio- and Diastereoselective Synthesis of
Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities |
| title_full_unstemmed | Facile, Regio- and Diastereoselective Synthesis of
Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities |
| title_short | Facile, Regio- and Diastereoselective Synthesis of
Spiro-Pyrrolidine and Pyrrolizine Derivatives and Evaluation of Their Antiproliferative Activities |
| title_sort | facile regio and diastereoselective synthesis of spiro pyrrolidine and pyrrolizine derivatives and evaluation of their antiproliferative activities |
| topic | QD1-999 Chemistry R735-854 Medical education. Medical schools. Research |
| url | http://eprints.usm.my/39099/1/Facile%2C_Regio-_and_Diastereoselective_Synthesis_of_Spiro-Pyrrolidine_and.pdf |
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