15 引文 斯高帕斯(Scopus)

摘要

A series of 1-aroylindoline-hydroxamic acids have been synthesized in the present study. The results of the biological evaluation led to the identification of compound 12 as dual HDAC6/HSP90 inhibitor. Compound 12 displayed striking inhibitory effects towards the HDAC6 isoform and HSP 90 protein with IC50 values of 1.15 nM (HDAC6) and 46.3 nM (HSP90). Compound 12 also exhibited 113, 139 and 246 fold higher selectivity for HDAC6 over HDAC 1, HDAC 3 and HDAC 8 isoforms and was endowed with significant cytotoxic effects with GI50 values ranging 1.04–1.61 μM against lung A549, colorectal HCT116, leukemia HL60, and EGFR T790M mutant lung H1975 cell lines. Another interesting finding of the study was substantial cytotoxic effects of compounds particularly against lung H1975 (NSCLC) cell lines with IC50 = 0.26 μM which may be mediated through HSP90 inhibition. Compound 8 as such was devoid of HDAC inhibitory activity.
原文英語
頁(從 - 到)667-677
頁數11
期刊European Journal of Medicinal Chemistry
150
DOIs
出版狀態已發佈 - 四月 25 2018

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

指紋 深入研究「1-Aroylindoline-hydroxamic acids as anticancer agents, inhibitors of HSP90 and HDAC」主題。共同形成了獨特的指紋。

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