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

Background: The rationale behind the study involved that in individuality benzimidazole-based 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(dlimidazol-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 mu M against HCT1 16 cell line and 5.15 pM against H460 cell line. Conclusion: The research fruitfully rejuvenates the potentials and importance of small molecular weight ligands for experimental oncology.