Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents

被引：105

作者：

Majeed, Rabiya ^{[1
,2
]}

Sangwan, Payare L. ^{[1
]}

Chinthakindi, Praveen K. ^{[1
]}

Khan, Imran ^{[1
]}

Dangroo, Nisar A. ^{[1
]}

Thota, Niranjan ^{[1
]}

Hamid, Abid ^{[2
]}

Sharma, Parduman R. ^{[2
]}

Saxena, Ajit K. ^{[2
]}

Koul, Surrinder ^{[1
]}

机构：

[1] CSIR Indian Inst Integrat Med, Bioorgan Chem Div, Jammu 180001, Jammu & Kashmir, India

[2] CSIR Indian Inst Integrat Med, Canc Pharmacol Div, Jammu 180001, Jammu & Kashmir, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

关键词：

Betulinic acid 1,2,3-trizole derivatives; Click chemistry; Cytotoxicity; DNA fragmentation; Apoptosis; CANCER; DERIVATIVES; TRITERPENOIDS; CHEMISTRY; PATHWAYS;

D O I：

10.1016/j.ejmech.2013.03.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic add, through concise 1,2,3-triazole synthesis via click chemistry approach at C-3position in ring A have been evaluated for their cytotoxic potentiation against nine human cancer cell lines. Most of the derivatives have shown higher cytotoxic profiles than the parent molecule. Two compounds i.e. 3 {1N(2-cyanophenyl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (7) and 3{1N(5-hydroxy-naphth-1yl)-1H-1,2,3-triazol-4yl}methyloxy betulinic acid (13) displayed impressive IC50 values (2.5 and 3.5 mu M respectively) against leukemia cell line HL-60 (5-7-fold higher potency than betulinic acid). As evident from various biological end points, inhibition of cell migration and colony formation, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis, is demonstrated. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：782 / 792

页数：11

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