Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents

被引：83

作者：

Abd El-Karim, Somaia S. ^{[1
]}

Anwar, Manal M. ^{[1
]}

Mohamed, Neama A. ^{[1
]}

Nasr, Tamer ^{[2
]}

Elseginy, Samia A. ^{[3
,4
]}

机构：

[1] Natl Res Ctr, Therapeut Chem Dept, Cairo 12622, Egypt

[2] Helwan Univ, Dept Pharmaceut Chem, Fac Pharm, Cairo 11795, Egypt

[3] Natl Res Ctr, Green Chem Dept, Cairo 12622, Egypt

[4] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Cardiff CF10 3NB, S Glam, Wales

来源：

BIOORGANIC CHEMISTRY | 2015年 / 63卷

关键词：

Anticancer; Molecular docking; Benzofuran; Pyrazole; PHARMACOLOGICAL EVALUATION; DRUG DISCOVERY; SRC; POTENT; INHIBITION; CYTOTOXICITY; ACTIVATION; APOPTOSIS; ZAP-70; CANCER;

D O I：

10.1016/j.bioorg.2015.08.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5) M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI(50): 1.00-2.71 mu M). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10 mu M. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiis rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：1 / 12

页数：12

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