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Synthesis and Microtubule‐Destabilizing Activity of N ‐Cyclopropyl‐4‐((3,4‐dihydroquinolin‐1(2 H )‐yl)sulfonyl)benzamide and its Analogs
Author(s) -
Field Jessica J.,
Singh A. Jonathan,
Sinha Saptarshi,
Rowe Matthew R.,
Denny William A.,
Brooke Darby G.,
Miller John H.
Publication year - 2019
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201801313
Subject(s) - efflux , benzamide , chemistry , amide , microtubule , carboxylic acid , aryl , multiple drug resistance , stereochemistry , p glycoprotein , cell culture , biochemistry , biology , microbiology and biotechnology , antibiotics , alkyl , genetics , organic chemistry
While clinically useful, microtubule‐targeting agents are limited by factors that include their susceptibility to multidrug resistance. A series of aryl sulfonamides, terminally substituted with an amide or carboxylic acid, was synthesized and assayed for biological activity in two human cancer cell lines. The resulting antiproliferative activity data demonstrated that an amide was superior to a carboxylic acid in the para position. The most potent compound ( 3 ) had an IC 50 for growth inhibition in the low micromolar range, caused cells to accumulate in G 2 M of the cell cycle, and led to depolymerization of microtubules. It was also not susceptible to the P‐glycoprotein drug efflux pump that underpins the resistance of cells to long‐term drug treatment schedules.