Design, synthesis and evaluation of novel hybrids between 4-anilinoquinazolines and substituted triazoles as potent cytotoxic agents

被引：23

作者：

Giang Le-Nhat-Thuy ^{[1
,2
]}

Thuy Van Dinh ^{[2
]}

Hai Pham-The ^{[3
]}

Hung Nguyen Quang ^{[3
]}

Nga Nguyen Thi ^{[2
]}

Tuyet Anh Dang Thi ^{[1
,2
]}

Phuong Hoang Thi ^{[1
]}

Tu Anh Le Thi ^{[1
]}

Ha Thanh Nguyen ^{[1
]}

Phuong Nguyen Thanh ^{[4
]}

Trung Le Duc ^{[4
]}

Tuyen Van Nguyen ^{[1
,2
]}

机构：

[1] Vietnam Acad Sci & Technol, Inst Chem, 18 Hoang Quoc Viet, Hanoi, Vietnam

[2] Vietnam Acad Sci & Technol, Grad Univ Sci & Technol, 18 Hoang Quoc Viet, Hanoi, Vietnam

[3] Hanoi Univ Pharm, 13-15 Le Thanh Tong, Hanoi, Vietnam

[4] Chu Van An High Sch, 10 Thuy Khue, Hanoi, Vietnam

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 23-24期

关键词：

4-Anilinoquinazolines; Triazole; Hybrids; Cytotoxic agents; EGFR inhibitors; FACTOR RECEPTOR EGFR; BIOLOGICAL EVALUATION; LUNG-CANCER; KINASE DOMAIN; INHIBITORS; GROWTH; DERIVATIVES; ANTICANCER; QUINAZOLINES; DISCOVERY;

D O I：

10.1016/j.bmcl.2018.10.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this research several series of novel dioxygenated ring fused 4-anilinoquinazolines (10a-d) and 4-anilinoquinazoline-substituted triazole hybrid compounds (11-14) have been designed and synthesized. Their biological significance was highlighted by evaluating in vitro for anticancer activities, wherein several compounds displayed excellent activity specifically against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). Especially, compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib. Docking the most cytotoxic compounds (11d, 13a, 13b, and 14c) into the ATP binding site of different EGFR tyrosine kinase domains was perfomed to predict the analogous binding mode of these compounds to the EGFR targets.

引用

页码：3741 / 3747

页数：7

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