Screening of Drug Efficacy of Rosmarinic Acid Derivatives as Aurora Ki-nase Inhibitors by Computer-Aided Drug Design Method

Background: Aurora kinases (AKs) belong to the serine/threonine kinase family and play a crucial role in regulating the cell cycle. Therefore, AKs are the hopeful target for anticancer therapies and these findings have encouraged researchers to rigorously hunt small molecule aurora kinase inhibitors, not only for research articles but also for use as therapeutic agents. Objective: The present study helps us to identify and screen the best phytochemicals as potent inhibitors against AKs. These potent inhibitors come from the various substitution of rosmarinic acid (RA). Methods: In this paper, we choose different tested derivative compounds for designing anticancer drugs by substituting various functional groups of standard drug RA. In silico studies were carried out to appreciate better drug candidature of some of these derivative compounds. This study was performed on 56 derived compounds of the standard RA. DFT study was conducted using the UB3LYP/6-311++G(d,p) basis set to study HOMO-LUMO energies, dipole moments, using the Gaussian16 suite. Some of the derived parameters, like ionization potential, electron affinity, softness-hardness, chemical potential, and electrophilicity index were noted. A docking study was performed with AKs inhibiting receptor using AutoDock 4.2. ADME prediction was made with the preADMET web tool. Molecular descriptor properties were predicted with molinspiration and OSIRIS property explorer. Results: Out of the 56 derivatives, 11 have passed all the rules of drug candidature, to serve as best AKs inhibitor, in a theoretical manner. Conclusion: This study should be supported by a new proposal to explore future studies with these 11 compounds against cancer.