Novel Benzimidazole Analogs as Inhibitors of EGFR Tyrosine Kinase

• Published in: Chemical biology & drug design Vol. 80; no. 4; pp. 625 - 630
• Main Authors: Yadav, Soni, Sinha, Deepa, Singh, Sanjay K., Singh, Vinay K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2012; Wiley
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; antitumor; benzimidazole; Benzimidazoles - chemistry; Benzimidazoles - pharmacokinetics; Benzimidazoles - pharmacology; Biochemistry & Molecular Biology; Breast - drug effects; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Cell Line, Tumor; Cell Survival - drug effects; Chemistry, Medicinal; EGFR; Female; Humans; Inhibitory Concentration 50; Life Sciences & Biomedicine; Mice; nanomolar; Pharmacology & Pharmacy; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - pharmacology; Rabbits; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Science & Technology; spectroscopy; nanomolar; antitumor; spectroscopy; DIHYDROFOLATE-REDUCTASE; ANTIBACTERIAL; benzimidazole; AGENTS; ANTIFUNGAL; ANTAGONISTS; DERIVATIVES; EGFR; QUINAZOLINES
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/j.1747-0285.2012.01407.x

A series of new benzimidazole congeners were synthesized, and their structures were elucidated on the basis of elemental analyses and spectral studies (1H NMR, FT‐IR and EI‐MS). Preliminary pharmacokinetic studies showed a promising outlook for further in vivo evaluation. The newly synthesized compounds were tested in vitro on human breast carcinoma cell line (MCF‐7) in which EGFR is highly expressed. Most of the tested compounds exhibited antitumor activity with IC50 values in the micro to nano molar range. A series of new benzimidazole congeners were synthesized and evaluated for egfr activity. Most of the tested compounds exhibited potent inhibitory activity against MCF‐7 cell line with IC50 values in the micro to nano molar range. These preliminary results were also evaluated by radio‐chemical methods for validation for discovery of potent antitumor agent.