Cancer and especially a breast cancer is a devastating health burden. Numerous approved therapies have proven beneficial in the treatment of breast cancer. However, resistance, serious adverse effects and remission due to limited efficacy needed a pursuit of newer effective agents. Substituted imidazole derivatives have been reported to possess antiproliferative activity. The present work is about the synthesis of a library of novel 2,4,5-triaryl-1H-imidazole derivatives. The synthesized compounds were screened for their anticancer activity against cancer cell line (MCF-7) by the MTT assay and many of them showed significant activity. Three compounds among the series have exhibited better antiproliferative activity due to presence of chromen-4-one and indole moiety attachment at 2nd position compared to the standard drug anastrazole. Furthermore, an in-silico molecular docking study has been performed against cyclin-dependent kinase to know the binding modes of these molecules and to further help the design of more promising agents. The compounds with chromen-4-one, quinoline-4-one and indolyl substituents referred to as CTI1, CTI3, and GTI9, respectively have been reported to possess promising anticancer activity.