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

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 erlot...

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Bibliographic Details
Published inPolycyclic aromatic compounds Vol. 43; no. 1; pp. 444 - 455
Main Authors Celik, Ismail, Ayhan-Kilcigil, Gulgun, Guven, Berna, Kara, Zumra, Onay-Besikci, Arzu
Format Journal Article
LanguageEnglish
Published Philadelphia Taylor & Francis 02.01.2023
Taylor & Francis Ltd
Subjects
Benzimidazole
Benzimidazoles
bis-thiosemicarbazide
bis-triazole
EGFR inhibitor activity
Epidermal growth factor
Epidermal growth factor receptors
Growth factors
Hydrogen bonds
Kinases
MM-GBSA
Molecular docking
Protein-tyrosine kinase receptors
Receptors
Thiosemicarbazides
Triazoles
Tyrosine
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Summary: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.
ISSN:1040-6638
1563-5333
DOI:10.1080/10406638.2021.2015404