Title:Screening of Drug Efficacy of Rosmarinic Acid Derivatives as Aurora Kinase Inhibitors by Computer-Aided Drug Design Method
Volume: 17
Issue: 5
Author(s): Kaushik Sarkar, Subhajit Sarkar and Rajesh Kumar Das*
Affiliation:
- Department of Chemistry, University of North Bengal, Darjeeling, West Bengal 734013,India
Keywords:
Aurora kinase inhibitor, rosmarinic acid, molecular docking, DFT, HOMO-LUMO, ADME prediction, molecular
descriptor properties.
Abstract:
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.
