Barukial Pratyashee, Nandi Rajib, Das Nipu Kumar, Barman Rituraj, Ahmed Benzir, Nagendraprasad Gunolla, Banerjee Tamal, Bezbaruah Bipul
Department of Applied Sciences, Gauhati University, Guwahati, 781014, Assam, India.
Center for the Environment, Indian Institute of Technology, Guwahati, 781039, Assam, India.
J Mol Model. 2025 May 21;31(6):167. doi: 10.1007/s00894-025-06385-w.
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.
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.
了解治疗性分子与体内受体之间的相互作用对于开发潜在的抗癌药物至关重要。近年来，吡唑衍生物因其在新型药物设计与发现中的显著药理特性，已逐渐成为重要的生物活性候选物。在此，我们运用量子化学计算、分子对接和分子动力学模拟，对一些具有潜在抗癌特性的选定吡唑衍生物进行了全面的计算和理论分析。
在本研究中，使用密度泛函理论（DFT），采用B3LYP泛函和6 - 31G(d,p)基组，在Gaussian16中进行量子化学计算，以研究吡唑衍生物的电子性质和分子间相互作用。进行自然键轨道（NBO）分析以探索电荷分布和供体 - 受体相互作用。同样，采用先进的拓扑分析方法，即约化密度梯度（RDG）、分子中的原子量子理论（QTAIM）、电子定位函数（ELF）、定位轨道指示器（LOL）和静电势（ESP），来表征分子间相互作用和电子密度特征。进行分子对接研究以评估吡唑衍生物与DNA（PDB ID：2m2c）的结合亲和力，特别关注与碱基对的相互作用。采用分子动力学模拟来研究长时间尺度上相互作用的稳定性和特征。这种综合方法整合了量子化学工具、分子对接和分子动力学模拟，以阐明吡唑衍生物与DNA核碱基之间的相互作用机制，增强它们作为抗癌药物的潜在新颖性。
