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Eur J Med Chem. 2018 Oct 5;158:733-742. doi: 10.1016/j.ejmech.2018.09.045. Epub 2018 Sep 15.

Conformation impacts on the bioactivities of SMART analogues.

Author information

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
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China. Electronic address: zuodaiying@163.com.
4
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China; Wuya College of Innovation, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China. Electronic address: kbao@syphu.edu.cn.
5
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: zhangweige@syphu.edu.cn.

Abstract

As promising colchicine binding site inhibitors, SMART and its analogues have attracted many research efforts in recent years. A large number of SMART analogues with different B-rings have been reported; however, the effects of B-ring on the bioactivity are still unclear so far. Herein, we speculated that the conformational preference caused by B-rings was crucial for active SMART analogues. Our assumption was supported by the molecular docking studies, molecular dynamic simulation and DFT computations of SMART and its analogues reported by other and our research groups. Moreover, several novel SMART analogues with different conformational preferences were designed and synthesized to disclose the conformation impacts, and the preliminary biological evaluation was in accordance with our assumption.

KEYWORDS:

CBSI; Conformation; DFT; Molecular modeling; Tubulin

PMID:
30245397
DOI:
10.1016/j.ejmech.2018.09.045
[Indexed for MEDLINE]

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