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

被引：39

作者：

Almansour, Abdulrahman I. ^{[1
]}

Kumar, Raju Suresh ^{[1
]}

Beevi, Farzana ^{[2
]}

Shirazi, Amir Nasrolahi ^{[3
,6
]}

Osman, Hasnah ^{[4
]}

Ismail, Rusli ^{[7
]}

Choon, Tan Soo ^{[5
]}

Sullivan, Brian ^{[3
]}

McCaffrey, Kellen ^{[3
]}

Nahhas, Alaa ^{[3
]}

Parang, Keykavous ^{[3
,6
]}

Ali, Mohamed Ashraf ^{[2
,5
]}

机构：

[1] King Saud Univ, Dept Chem, Coll Sci, Riyadh 11451, Saudi Arabia

[2] Sunrise Univ, Dept Med Chem, Alwar 301030, Rajasthan, India

[3] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA

[4] Univ Sains Malaysia, Sch Chem Sci, Minden 11800, Penang, Malaysia

[5] Univ Sains Malaysia, Inst Res Mol Med, Minden 11800, Penang, Malaysia

[6] Chapman Univ, Sch Pharm, Irvine, CA 92618 USA

[7] Univ Malaya, Ctr Excellence Res AIDS, Kuala Lumpur 50603, Malaysia

来源：

MOLECULES | 2014年 / 19卷 / 07期

关键词：

antiproliferative activity; diastereoselective synthesis; pyrrolizine; regio-selective synthesis; spiro-pyrolidine; DIVERSITY-ORIENTED SYNTHESIS; MULTICOMPONENT REACTIONS; REGIOSELECTIVE SYNTHESIS; 1,3-DIPOLAR CYCLOADDITION; 3-COMPONENT; DISCOVERY; ECONOMY;

D O I：

10.3390/molecules190710033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：10033 / 10055

页数：23

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