Discovery of Piperazin-2-yl-pyrimidines as Anticancer Agents via Targeting JNK Signaling Pathway in Human MCF-7 Breast Carcinoma

Breast cancer (BC) is the second leading cause of cancer-related mortality in women, and targeting biological pathways such as the JNK pathway has proven to be a viable therapeutic target for BC therapy. Here, we synthesized piperazin-2-yl-pyrimidines and evaluated them for anticancer activity against MCF-7 cells. In addition, antioxidant, reactive oxygen species (ROS) inhibition, caspase activity, and toxicity in platelets were studied in the presence and absence of active compound IA-6 or IA-7. Our detailed experimental analysis found that the compound IA-7 showed anticancer activity by either activating p-JNK or by inducing radical species in cancer and thrombosis model. Evident to in vitro analysis, the structure based molecular interaction studies of binding of IA-7 to JNK3S exhibited a significant binding energy of −7.56 kcal/mol which was found to be a better binder when compared to previously reported JNK inducer (PC-12). Overall, we herein report the analytically pure IA-7 as lead structure that could be used as a template to develop target based anticancer agents where JNK modulation is predominant.