Synthesis, Anticancer Evaluation and Docking Study of 3- Benzyloxyhydantoin Derivatives

Author(s):

Jun Liu, Kai Zhang, Xi Mai, Jinjin Wei, Yijing Liao, Ying Zhong, Yang Liu, Lihua Feng and Chao LiuPages 37-47 (11)

Abstract:

A series of 3-benzyloxyhydantoin derivatives were designed and synthesized by introducing hydroxyurea pharmacophore into hydantoin rigid scaffold. The cytotoxic activities of the target compounds were evaluated in vitro against three cancer cell lines. Compounds 5b, 5c, 5e, 5g, 6c and 6g displayed high activity on all of the three cancer cell lines and the most promising compounds were 5g, 6g with IC50 values of 0.04 and 0.01µM. Binding of derivatives for the ribonucleotide reductase (RR) was investigated by use of molecular docking studies. Our findings show that modification at the C5 position of hydantoin with isopropyl or isobutyl was favorable to increasing binding affinity to the active site of the RR receptor and antiproliferative activity.

Keywords:

Molecular modeling, ribonucleotide reductase, anticancer, synthesis, MTT Assay, benzyloxyhydantoin derivatives.

Affiliation:

School of Pharmacy, Nanchang University, 461 Nanchang 330006, China.

Graphical Abstract:

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