Background: A newer trend has been seen recently to reuse the conventional drugs with
distinct indications for the newer applications to speed up the drug discovery and development
based on earlier records and safety data. Most of the non-cancerous agents could afford a little or
tolerable side effects in individuals. However, the repositioning of these non-cancerous agents for
successful anticancer therapy is an outstanding strategy for future anti-cancer drug development.
Since more diverse and selective cancer drug targets are being discovered and developed, the approved
drug collections are particularly useful to quickly identify clinically advanced anticancer
drugs against those targets.
Objective: Antihelminthic drugs such as Mebendazole and Albendazole (Benzimidazole class)
have been reported to exhibit cytotoxicity (or anticancer activities) against several types of cancer.
Therefore, this study aims to repurpose the benzimidazole scaffold for breast cancer treatment.
Methods: In the present study, three hydrazone analogs having a benzimidazole motif in their structural
frame were synthesized. Their in-silico binding studies against HER2 receptor (PDB ID:
4LQM) and ADMET studies were carried out using Accelrys drug discovery studio 4.1. Cytotoxicity
of the synthesized compounds against HER2 overexpressed MCF-7 cell lines was determined by
Results: One of the compounds 2-[2-(2,4-dinitrophenyl)hydrazinylidene]-2,3-dihydro-1H-benzimidazole
(U1) has shown good cytotoxicity when compared to the standard Lapatinib, which is a well
known HER2 inhibitor.
Conclusions: Thus, the designed benzimidazole scaffold might serve as the best leads for treating
breast cancer, which is additionally confirmed by performing their docking study via Accelrys discovery