title: Synthesis, cytotoxicity, docking study, and tubulin polymerization inhibitory activity of novel 1-(3,4-dimethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxanilides.
abstract: A series of novel 1-(3,4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-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 IC50 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.
authors.affiliation: Faculty of Pharmacy, Medicinal Chemistry Department, Minia University, Minia, Egypt.
authors.forename: Omar M
authors.initials: OM
authors.lastname: Aly
authors.forename: Eman A
authors.initials: EA
authors.lastname: Beshr
authors.forename: Raed M
authors.initials: RM
authors.lastname: Maklad
authors.forename: Muhamad
authors.initials: M
authors.lastname: Mustafa
authors.forename: Amira M
authors.initials: AM
authors.lastname: Gamal-Eldeen
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000813:Anilides; D014230:Triazoles; D050257:Tubulin Modulators; D003078:Colchicine
keywords: 1,2,4-Triazole; Cytotoxicity; Docking study; Tubulin