Synthesis, Biological Investigation and Docking Study of Novel Chromen Derivatives as Anti-Cancer Agents

Background: According to the latest global cancer data, cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018. Among that female breast cancer ranks as the fifth leading cause of death (627000 deaths, 6.6%). The main causative factor involved in breast cancer development and progression is the Estrogen Receptor (ER) which is the essential target for anti-cancer drug discovery. Since millennia ER-α has been considered as an oncology mark for the treatment of breast cancer. Methods: A series of novel 6-methyl-3-(3-oxo-1-phenyl-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)propyl)-2Hchromen- 2-one was designed, synthesized and screened for their anti-breast cancer activity against estrogen receptor-positive MCF-7, ZR-75-1 and negative MDA-MB-435 human breast cancer cell lines. Estrogen level of all the potent cytotoxic compounds were measured on day 30 of intoxication was compared with the control and N-methyl-N-nitrosourea (MNU) group. The docking study was performed to predict binding orientation towards the estrogen receptor-α. Results: Among the synthesized compounds C-3, C-5 and C-15 were showing potent cytotoxicity against estrogen receptor-positive MCF-7. The potent cytotoxic compounds C-3, C-5 and C-15 were further evaluated for in vivo anti-cancer activity by MNU induced mammary carcinoma in female sprague-dawley rats. The in vivo anticancer activity result shows that the compound C-5 has protuberant affinity towards estrogen receptor as standard TAM (Tamoxifen). The docking of the synthesized chromen derivatives showed interaction modes comparable to that of the co-crystallized ligands. Conclusion: The designed class has very promising starting point for the development and further improvement in anti-breast cancer class of drugs.