Multi-spectroscopic, thermodynamic, and molecular docking/dynamic approaches for characterization of the binding interaction between calf thymus DNA and palbociclib

Author:

Magdy Galal,Shaldam Moataz A.,Belal Fathalla,Elmansi Heba

Abstract

AbstractStudying the binding interaction between biological macromolecules and small molecules has formed the core of different research aspects. The interaction of palbociclib with calf thymus DNA at simulated physiological conditions (pH 7.4) was studied using different approaches, including spectrophotometry, spectrofluorimetry, FT-IR spectroscopy, viscosity measurements, ionic strength measurements, thermodynamic, molecular dynamic simulation, and docking studies. The obtained findings showed an apparent binding interaction between palbociclib and calf thymus DNA. Groove binding mode was confirmed from the findings of competitive binding studies with ethidium bromide or rhodamine B, UV–Vis spectrophotometry, and viscosity assessment. The binding constant (Kb) at 298 K calculated from the Benesi–Hildebrand equation was found to be 6.42 × 103 M−1. The enthalpy and entropy changes (∆H0 and ∆S0) were − 33.09 kJ mol−1 and 61.78 J mol−1 K−1, respectively, showing that hydrophobic and hydrogen bonds constitute the primary binding forces. As indicated by the molecular docking results, palbociclib fits into the AT-rich region of the B-DNA minor groove with four base pairs long binding site. The dynamic performance and stability of the formed complex were also evaluated using molecular dynamic simulation studies. The in vitro study of the intermolecular binding interaction of palbociclib with calf thymus DNA could guide future clinical and pharmacological studies for the rational drug scheming with enhanced or more selective activity and greater efficacy.

Funder

Kafr El Shiekh University

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

Reference68 articles.

1. National Center for Biotechnology Information. PubChem Compound Summary for CID 5330286, Palbociclib. https://pubchem.ncbi.nlm.nih.gov/compound/Palbociclib. Accessed 18 February 2022.

2. Center for drug evaluation and research. 207103Orig1s000 (2022).

3. Liu, M., Liu, H. & Chen, J. Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment. Oncol. Rep. 39, 901–911 (2018).

4. MedlinePlus, National Library of Medicine (US) (2022).

5. Serra, F. et al. Palbociclib in metastatic breast cancer: Current evidence and real-life data. Drugs Context 8, 212579 (2019).

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3