Synergistic in silico exploration of some pyrazole-based potential anticancer agents: a DFT, molecular docking, and molecular dynamics study

Abstract

Context

Understanding the interaction between therapeutic molecules with in vivo receptors is very essential in developing potential anticancer agents. In recent years, pyrazole derivatives have been evolving as a significant bioactive candidate due to their remarkable pharmacological properties in novel drug design and discovery. Herein, we present a comprehensive computational and theoretical analysis of some selected pyrazole derivatives with potential anticancer properties, employing quantum chemical calculations, molecular docking, and molecular dynamics simulation.

Method

In this study, quantum chemical calculations were employed using density functional theory (DFT) with B3LYP functional and 6–31G(d,p) basis set in Gaussian16 to investigate the electronic properties and intermolecular interactions of pyrazole derivatives. Natural bond orbital (NBO) analysis was performed to explore charge distribution and donor–acceptor interactions. Similarly, advanced topological analyses, viz., reduced density gradient (RDG), quantum theory of atoms in molecules (QTAIM), electron localisation function (ELF), localised orbital indicator (LOL), and electrostatic potential (ESP), to characterise intermolecular interactions and electron density features. Molecular docking studies were conducted to assess the binding affinity of the pyrazole derivatives with DNA (PDB ID: 2m2c), specifically focussing on interactions with base pairs. Molecular dynamics simulations were employed to examine the stability and characteristics of interactions over a prolonged timescale. This comprehensive approach integrates quantum chemical tools, molecular docking, and molecular dynamics simulations to elucidate the interaction mechanisms between pyrazole derivatives and DNA nucleobases, enhancing their potential novelty as anticancer agents.

Graphical abstract