title: Synthesis, Anticancer Evaluation and Docking Study of 3- Benzyloxyhydantoin Derivatives.
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.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nanchang University, 461 Nanchang 330006, China. maixi123@aliyun.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Mai
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Nanchang University, 461 Nanchang 330006, China. jingzi5027@126.com.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Liao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhong
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Lihua
authors.initials: L
authors.lastname: Feng
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006827:Hydantoins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D020014:K562 Cells; D051379:Mice; D062105:Molecular Docking Simulation; D012264:Ribonucleotide Reductases / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006827:Hydantoins; D029701:Saccharomyces cerevisiae Proteins; D012264:Ribonucleotide Reductases