title: Structure-based drug design and biological evaluation of 2-acetamidobenzothiazole derivative as EGFR kinase inhibitor.
abstract: EGFR tyrosine kinase has been reported mainly in 40-80% of non-small lung cancers, in addition to colon and breast cancers. In this study, we illustrate the synthesis of a highly potent antitumor agent. The synthesized compound 4 was screened at NCI, USA, for antitumor activity against non-small lung cancer, colon cancer and breast cancer cell lines. Results indicated that this compound is more potent antitumor agent compared to erlotinib against all tested cell lines except breast cancer (MDA-MB-468) cell line. In addition, it was tested initially at a single dose concentration of 100 µM over 11 different kinases. At this concentration, 94.45% inhibition of the enzymatic activity of EGFR kinase was observed, while the inhibition in activity was below 55% in all other kinases. Compound 4 was further tested in a 10-dose IC50 mode and showed IC50 value of 0.239 µM for EGFR kinase. In vivo acute toxicity of this compound was also tested.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University , Mansoura , Egypt.
authors.forename: Moustafa T
authors.initials: MT
authors.lastname: Gabr
authors.forename: Nadia S
authors.initials: NS
authors.lastname: El-Gohary
authors.forename: Eman R
authors.initials: ER
authors.lastname: El-Bendary
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: El-Kerdawy
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D047428:Protein Kinase Inhibitors; C000601201:ethyl 1-(2-((6-chlorobenzothiazol-2-yl)amino)-2-oxoethyl)-5-hydroxy-1H-pyrazole-4-carboxylate; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Acetamidobenzothiazole; EGFR tyrosine kinase inhibitor; breast cancer; colon cancer; in vivo acute toxicity; non-small lung cancer