Synthesis of 5-substituted-1H-pyrazolo [4,3-d] pyrimidin-7(6H)-one analogs and their biological evaluation as anticancer agents: mTOR inhibitors

被引：36

作者：

Reddy, G. Lakshma ^{[1
,4
]}

Guru, Santosh Kumar ^{[2
]}

Srinivas, M. ^{[1
,4
]}

Pathania, Anup Singh ^{[2
,4
]}

Mahajan, Priya ^{[3
,4
]}

Nargotra, Amit ^{[3
,4
]}

Bhushan, Shashi ^{[2
,4
]}

Vishwakarma, Ram A. ^{[1
,4
]}

Sawant, Sanghapal D. ^{[1
,4
]}

机构：

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

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

[3] Indian Inst Integrat Med, CSIR, Jammu 180001, India

[4] Acad Sci & Innovat Res, New Delhi, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 80卷

关键词：

Pyrazolo[4,3-d]pyrimidin-7(6H)-one; K2S2O8; catalyst; Microwave irradiation; Cytotoxicity; mTOR inhibitor; LEUKEMIA HL-60 CELLS; PYRAZOLOPYRIMIDINES; ANTAGONISTS; METABOLISM; ENHANCE;

D O I：

10.1016/j.ejmech.2014.04.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A microwave assisted strategy for synthesis of series of 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones has been developed and their biological evaluation as anticancer agents is described. The synthetic protocol involves simple procedure by oxidative coupling of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide with different aldehydes in presence of K2S2O8 offering 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one compounds in excellent yields. The in vitro anticancer activity screening against human cancer cell lines HeLa, CAKI-I, PC-3, MiaPaca-2, A549 gave good results. The in detailed mechanistic correlation studies of compound 3m revealed that the compound shows anticancer activity through apoptosis mechanism and also inhibits mTOR with nonomolar potency. The design was based on docking with mTOR protein. The concentration dependent cell cycle analysis, western blotting experiment and nuclear cell morphology studies have been described. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：201 / 208

页数：8

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