2. Academic Validation
  3. Design, synthesis and evaluation of antiproliferative and antitubulin activities of 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles

Design, synthesis and evaluation of antiproliferative and antitubulin activities of 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles

  • Bioorg Chem. 2020 Nov;104:103909. doi: 10.1016/j.bioorg.2020.103909.
Chao Wang 1,  Yuelin Li 1,  Tong Liu 2,  Zeyu Wang 3,  Yujing Zhang 1,  Kai Bao 3,  Yingliang Wu 2,  Qi Guan 4,  Daiying Zuo 5,  Weige Zhang 6
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
  • 2 Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
  • 3 Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: guanqi@syphu.edu.cn.
  • 5 Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: zuodaiying@163.com.
  • 6 Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address: zhangweige2000@sina.com.
PMID: 33142419 DOI: 10.1016/j.bioorg.2020.103909
Abstract

A series of novel 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles possessing 1,2,4-triazole as the hydrogen-bond acceptor were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Some of them exhibited moderate activities in vitro against the three Cancer cell lines including SGC-7901, A549 and HeLa. Compound 6e exhibited the highest potency against the three Cancer cell lines. Moreover, the tubulin polymerization experiments indicated that compound 6e could inhibit the tubulin polymerization. Immunofluorescence study and cell cycle analysis clearly revealed compound 6e could disrupt intracellular microtubule organization, arrest cell cycle at the G2/M phase. In addition, molecular docking analysis demonstrated the interaction of compound 6e at the colchicine-binding site of tubulin. These preliminary results suggested that compound 6e is a new colchicine binding site inhibitor and worthy of further investigation.

Keywords

1,2,4-triazole; Antiproliferative activity; Colchicine binding site inhibitor; Molecular docking.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z