N-(2-(1H-benzo[d]imidazol-2-yl)Phenyl)-2- (Substituted-styryl)Aniline as Anti-proliferative Agents: Rejuvenating the Importance of Low Molecular Weight Ligands in Oncotherapeutics

Abstract:

Background: The rationale behind the study involved that in individuality benzimidazolebased molecules demonstrates significant anti-proliferative activity; chalcone molecules like xanthohumol are known to express noteworthy anti-cancer activity; benzamide derived products show remarkable inhibition of HDAC (an emerging anti-proliferative target) and styrene-based compounds possesses notable anti-tumor activity. Materials and Methods: In this research, an attempt was made to synthesize and characterize a series of hybridized molecules of the prototype (E)-N-(2-(1H-benzo[d]imidazol-2-yl) phenyl)-2-(substituted-styryl)aniline which comprises of a benzimidazole function; along with a chalcone (or styryl) moiety linked by a benzamide. The study involved screening of the novel derivatives against non-small cell lung cancer cell line (H460; ATCC: HTB177) and human colorectal cancer cell line (HCT116; ATCC: CCL-247) using Propidium Iodide assay. In silico docking study was also performed against protein tyrosine kinase (PDB ID: 2J5F) to determine the probable mechanism of action of the novel compounds. Results: The study reflected the profound role and positions of substitution on the phenyl moiety of the benzimidazole system. The compound DSTYR4 displayed most potent antiproliferative activity with IC₅₀ values of 2.98 μM against HCT116 cell line and 5.15 μM against H460 cell line. Conclusion: The research fruitfully rejuvenates the potentials and importance of small molecular weight ligands for experimental oncology.

Key words: Benzimidazole, Benzamide, Styryl, Chalcone, Hybrid, Anti-proliferative.