Synthesis of Hybrids of Dihydropyrimidine and Pyridazinone as potential Anti-Breast Cancer Agents

Background: Different 3-aroylpropionic acids and dihydropyrimidine hydrazine derivatives were condensed together to yield a series of dihydropyrimidine and pyridazinone hybrids (5a-u). Objective: This was done in order to develop therapeutic agents for the treatment of breast cancer with improved Cycloxygenase-2 (COX-2) selectivity. In-vitro anticancer evaluation for these compounds was done against human breast cancer cell lines (MCF-7, MDA-MB-231) and normal human keratinocytes (HaCaT). Conclusion: Amongst all the developed analogs, compound 5l emerged as the most potent agent against both these cell lines with IC50 values of 3.43 and 2.56 mu M respectively. The synthesized compounds were also evaluated for COX-2 selectivity. To observe the binding pattern of the compounds with COX-2, a docking study was performed using PDB ID: 1CX2.