当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Colorectal anticancer activities of polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamides.

Colorectal anticancer activities of polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamides.

Abstract：

:To develop potent chemotherapeutic agents for treating colorectal cancers, polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamide derivatives were designed. Twenty-two novel derivatives were synthesized and their cytotoxicities were measured using a clonogenic long-term survival assay. Of these derivatives, 3-(1-hydroxynaphthalen-2-yl)-N-(3-methoxyphenyl)-5-(4-methoxyphenyl)-pyrazoline-1-carbothioamide (NPC 15) exhibited the best half-maximal cell growth inhibitory concentrations (196.35nM). To explain its cytotoxicity, further biological experiments were performed. Treatment with NPC 15 inhibited cell cycle progression and triggered apoptosis through the caspase-mediated pathway. Its inhibitory effects on several kinases participating in the cell cycle were investigated using an in vitro kinase assay. Its half-maximal inhibitory concentrations for aurora kinases A and B were 105.03μM and 8.53μM, respectively. Further analysis showed that NPC 15 decreased phosphorylation of aurora kinases A, B, and C and phosphorylation of histone H3, a substrate of aurora kinases A and B. Its molecular binding mode for aurora kinase B was elucidated using in silico docking. In summary, polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamides could be potent chemotherapeutic agents.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Shin SY,Ahn S,Yoon H,Jung H,Jung Y,Koh D,Lee YH,Lim Y

doi

10.1016/j.bmcl.2016.07.037

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

4301-9

issue

17

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30750-8

journal_volume

26

pub_type

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