In Vitro and in Silico Evaluation of Some New 1H-Benzimidazoles Bearing Thiosemicarbazide and Triazole as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

Abstract

A new class of benzimidazole derivatives bearing bis-triazole or bis-thiosemicarbazide structure was designed and synthesized as potential inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase. In vitro EGFR kinase enzyme inhibition properties were determined in comparison with erlotinib and compound (6b) containing propyl side chain at the 4th position of triazole rings showed 13.8% inhibition. Molecular docking studies were performed and docking score and binding energy were established. The most active compound formed a hydrogen bond between the Asn818 and triazole NH at the 2nd position of the benzimidazole skeleton. Predicted ADME profiles of the compounds were calculated and found to be within the appropriate reference ranges.

Graphical Abstract

Keywords:

• Benzimidazole
• bis-triazole
• bis-thiosemicarbazide
• EGFR inhibitor activity
• molecular docking
• MM-GBSA

Acknowledgments

The Central Laboratory of the Faculty of Pharmacy of Ankara University and Erciyes University Technology and Research Center (TAUM) supported the acquisition of the NMR and mass spectra and elemental analyses in this work.

Disclosure statement

The authors proclaim that they have no contradiction of interest.

Additional information

Funding

This study was funded by Ankara Universitesi BAP-20H0237001.