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Synthesis, Cytotoxicity, Docking Study, and Tubulin Polymerization Inhibitory Activity of Novel 1‐(3,4‐Dimethoxyphenyl)‐5‐(3,4,5‐trimethoxyphenyl)‐1 H ‐1,2,4‐triazole‐3‐carboxanilides
Author(s) -
Aly Omar M.,
Beshr Eman A.,
Maklad Raed M.,
Mustafa Muhamad,
GamalEldeen Amira M.
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400096
Subject(s) - chemistry , tubulin , cytotoxicity , microtubule , colchicine , stereochemistry , in vitro , docking (animal) , triazole , amino acid , cell culture , biochemistry , biology , organic chemistry , medicine , genetics , nursing , microbiology and biotechnology
A series of novel 1‐(3,4‐methoxyphenyl)‐5‐(3,4,5‐trimethoxyphenyl)‐1 H ‐1,2,4‐triazole‐3‐carboxylic acid derivatives ( 4a – n ) were synthesized and evaluated for their in vitro cytotoxic activity against the growth of four different human cell lines (hepatocarcinoma HepG2, breast adenocarcinoma MCF‐7, colon carcinoma DLD‐1, and leukemia HL‐60). The anilides of m ‐anisidine 4e , o ‐anisidine 4f , and 3,5‐difluoroaniline 4l demonstrated best results on MCF‐7 cells and mean IC 50 values of 7.79, 10.79, and 13.20 µM, respectively. The compounds produced a significant reduction in cellular microtubules at a concentration of 25 µg/mL, for microtubule loss. Molecular modeling studies involving compounds 4d , 4e , 4f , and 4l with the colchicine binding site of α,β‐tubulin revealed hydrogen bonding and hydrophobic interactions with several amino acids in the colchicine binding site of β‐tubulin.