Title:Synthesis of Hybrids of Dihydropyrimidine and Pyridazinone as potential Anti-Breast Cancer Agents
Volume: 18
Issue: 4
Author(s): Wasim Akhtar, Garima Verma, Mohemmed Faraz Khan, Mohammad Shaquiquzzaman, Arpana Rana, Tarique Anwer, Mymoona Akhter and M. Mumtaz Alam*
Affiliation:
- Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062,India
Keywords:
Anticancer agent, breast cancer, COX-2 inhibitors, cyanopyrimidne, hybrid, pyridazinone.
Abstract: 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 µM 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.
