TY - JOUR
T1 - Facile, regio- And diastereoselective synthesis of spiro-pyrrolidine and pyrrolizine derivatives and evaluation of their antiproliferative activities
AU - Almansour, Abdulrahman I.
AU - Kumar, Raju Suresh
AU - Beevi, Farzana
AU - Shirazi, Amir Nasrolahi
AU - Osman, Hasnah
AU - Ismail, Rusli
AU - Choon, Tan Soo
AU - Sullivan, Brian
AU - McCaffrey, Kellen
AU - Nahhas, Alaa
AU - Parang, Keykavous
AU - Ali, Mohamed Ashraf
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Antiproliferative activity
KW - Diastereoselective synthesis
KW - Pyrrolizine
KW - Regio-selective synthesis
KW - Spiro-pyrolidine
UR - http://www.scopus.com/inward/record.url?scp=84904816609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904816609&partnerID=8YFLogxK
U2 - 10.3390/molecules190710033
DO - 10.3390/molecules190710033
M3 - Article
C2 - 25014532
AN - SCOPUS:84904816609
SN - 1420-3049
VL - 19
SP - 10033
EP - 10055
JO - Molecules
JF - Molecules
IS - 7
ER -