6 引文 斯高帕斯(Scopus)

摘要

We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC50 value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6). Some key interactions of 9 with the amino acid residues of the active site of tubulin and with amino acid residues of HDAC 1 isoform have been figured out by molecular modeling. Compound 9 also demonstrated significant in vivo efficacy in the human non-small cell lung cancer A549 xenograft model as well as B-cell lymphoma BJAB xenograft tumor model.
原文英語
頁(從 - 到)612-630
頁數19
期刊European Journal of Medicinal Chemistry
162
DOIs
出版狀態已發佈 - 一月 15 2019

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

指紋 深入研究「1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase」主題。共同形成了獨特的指紋。

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