Synthesis and biological evaluation of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3-triazole-4-carboxamides as antimitotic agents

被引:24
作者
Prasad, Budaganaboyina [1 ,2 ]
Nayak, V. Lakshma [1 ]
Srikanth, P. S. [1 ]
Baig, Mirza Feroz [1 ]
Reddy, N. V. Subba [1 ]
Babu, Korrapati Suresh [1 ,2 ]
Kamal, Ahmed [1 ,3 ]
机构
[1] Indian Inst Chem Technol, CSIR, Med Chem & Biotechnol, Hyderabad 500007, Andhra Pradesh, India
[2] Osmania Univ, Dept Chem, Hyderabad 500007, Telangana, India
[3] Jamia Hamdard, Sch Pharmaceut Educ & Res, New Delhi 110062, India
关键词
2-Anilino-3-aminopyridines; Triazole-4-carboxilic acids; Apoptosis; Cell cycle; Colchicine binding; Molecular docking; Tubulin polymerization; POTENTIAL ANTICANCER AGENTS; TUBULIN POLYMERIZATION; ANTITUBULIN AGENTS; MEDIATED APOPTOSIS; BINDING; DESIGN; CANCER; INHIBITORS; DERIVATIVES; COLCHICINE;
D O I
10.1016/j.bioorg.2018.11.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A library of 1-benzyl-N-(2-(phenylamino)pyridin-3-yl)-1H-1,2,3 triazole-4-carboxamides (7a-al) have been designed, synthesized and screened for their anti-proliferative activity against some selected human cancer cell lines namely DU-145, A-549, MCF-7 and HeLa. Most of them have shown promising cytotoxicity against lung cancer cell line (A549), amongst them 7f was found to be the most potent anti-proliferative congener. Furthermore, 7f exhibited comparable tubulin polymerization inhibition (IC50 value 2.04 mu M) to the standard E7010 (IC50 value 2.15 mu M). Moreover, flow cytometric analysis revealed that this compound induced apoptosis via cell cycle arrest at G(2)/M phase in A549 cells. Induction of apoptosis was further observed by examining the mitochondrial membrane potential and was also confirmed by Hoechst staining as well as Annexin V-FITC assays. Furthermore, molecular docking studies indicated that compound 7f binds to the colchicine binding site of the beta-tubulin. Thus, 7f exhibits anti-proliferative properties by inhibiting the tubulin polymerization through the binding at the colchicine active site and by induction of apoptosis.
引用
收藏
页码:535 / 548
页数:14
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