Synthesis and In Silico Studies of C-4 Substituted Coumarin Analogues as Anticancer Agents

Background: Coumarin is a fused ring system and possesses the enormous capability of targeting various receptors participating in the cancer pathway. Coumarin and its derivatives were found to exhibit very rare toxicity and other side effects. It has been found its immense anticancer potential depends on the nature of the group present and its pattern of substitution on the basic nucleus. Objectives: Synthesis of C-4 substituted coumarin derivatives and to study their molecular interactions with ERα for the anticancer activity for Breast Cancer. Methods: C-4 substituted coumarins analogues (1-10) have been synthesized using conventional heating and microwave irradiation. Using Schrodinger software, molecular modeling studies were carried out and ADME properties of the compounds were predicted. Results: All the synthesized compounds have shown better G-Score (-6.87 to -8.43 kcal/mol) as compared to the standard drug tamoxifen (-5.28kcal/mol) and auraptene (-3.89kcal/mol). Molecular docking suggests that all compounds fit in the active site of protein as they have the same hydrophobic pocket as standard drug tamoxifen, and have an acceptable range of ADME properties. Conclusion: Microwave-assisted synthesis showed better results as compared to conventional heating. In silico studies revealed that all the compounds befit in the active site of the protein. ADME properties showed that all compounds are in allowable limits for human oral absorption. In the future, there is a possibility of in vitro and in vivo studies of the synthesized compounds.