The Bcl-2 family’s anti-apoptotic proteins, particularly Mcl-1, offer a viable avenue for cancer treatment since cancer cells can undergo apoptosis when their selective suppression occurs. Mcl-1 is essential for controlling the advancement of the cell cycle, as well as apoptosis. There is a constant clinical need for more potent treatments for breast and ovarian malignancies, even with advancements in the discovery of anticancer drugs. By synthesizing cyanopyrimidine derivatives that demonstrate both dual inhibitory activity against Mcl-1 and Bcl-2, and successful cell cycle arrest, our research seeks to contribute to the development of innovative therapeutic medicines. We created a number of new 6-substituted cyanopyrimidines and tested their anticancer effects on SKOV-3 and MCF-7 cell lines as well as apoptosis and cell cycle arrest assays.

Following their synthesis in good to medium yields, pyrrole-pyrimidine-5-cyano scaffolds (2 and 4) were tested for anti-cancer efficacy using the MTT assay against ovarian cancer (SKOV-3) and breast cancer (MCF-7) cell lines. The IC50 values of 1031.135 µg/mL and 846.4994 μg/mL, respectively, were obtained from cytotoxicity assays conducted on the SKOV-3 and MCF-7 cell lines, which demonstrated a substantial decrease in cell viability. Apoptosis and Cell cycle arrest were also carried out to configure the primary contact with cancer cell lines, and N-pyrrole-pyrimidine-5-cyano 2a demonstrated the most anti-cancer efficacy against both tested cell lines in the in vitro assay. Additionally, the molecular docking research revealed that compound (2a) interacts significantly with active sites of Cyclin-dependent kinase 2 (CDK-2) (PDB: 5ANJ) and Cyclin-dependent kinase 6 (CDK-6) (PDB: 5LT2). In order to determine the primary method of action, enzymatic assays were also conducted on CDK2 and CDK6 utilizing specialized Enzyme-Linked Immunosorbent Assay (ELISA) Kits. Our findings indicated that compound (2a) has the potential to be an effective cancer treatment.