Exploring the effectiveness of flavone derivatives for treating liver diseases: Utilizing DFT, molecular docking, and molecular dynamics techniques

Syeda Tasnim Quayum; Nusrat Jahan Ikbal Esha; Siam Siraji; Sanaa S Al Abbad; Zainab H A Alsunaidi; Mansour H Almatarneh; Shofiur Rahman; Abdullah N Alodhayb; Khuloud A Alibrahim; Sarkar M A Kawsar; Kabir M Uddin

doi:10.1016/j.mex.2023.102537

Exploring the effectiveness of flavone derivatives for treating liver diseases: Utilizing DFT, molecular docking, and molecular dynamics techniques

MethodsX. 2023 Dec 29:12:102537. doi: 10.1016/j.mex.2023.102537. eCollection 2024 Jun.

Affiliations

¹ Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka 1217, Bangladesh.
² Department of Chemistry, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
³ Department of Chemistry, University of Jordan, Amman 11942, Jordan.
⁴ Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia.
⁵ Department of Chemistry, Princess Nora bint Abdulrahman University, College of Science, Riyadh, Al Riyadh, 11671, Saudi Arabia.
⁶ Lab of Carbohydrate and Nucleoside Chemistry, Department of Chemistry, University of Chittagong, Chittagong 4331, Bangladesh.

Abstract

In exploring nature's potential in addressing liver-related conditions, this study investigates the therapeutic capabilities of flavonoids. Utilizing in silico methodologies, we focus on flavone and its analogs (1-14) to assess their therapeutic potential in treating liver diseases. Molecular change calculations using density functional theory (DFT) were conducted on these compounds, accompanied by an evaluation of each analog's physiochemical and biochemical properties. The study further assesses these flavonoids' binding effectiveness and locations through molecular docking studies against six target proteins associated with human cancer. Tropoflavin and taxifolin served as reference drugs. The structurally modified flavone analogs (1-14) displayed a broad range of binding affinities, ranging from -7.0 to -9.4 kcal mol⁻¹, surpassing the reference drugs. Notably, flavonoid (7) exhibited significantly higher binding affinities with proteins Nrf2 (PDB:1 × 2 J) and DCK (PDB:1 × 2 J) (-9.4 and -8.1 kcal mol⁻¹) compared to tropoflavin (-9.3 and -8.0 kcal mol⁻¹) and taxifolin (-9.4 and -7.1 kcal mol⁻¹), respectively. Molecular dynamics (MD) simulations revealed that the docked complexes had a root mean square deviation (RMSD) value ranging from 0.05 to 0.2 nm and a root mean square fluctuation (RMSF) value between 0.35 and 1.3 nm during perturbation. The study concludes that 5,7-dihydroxyflavone (7) shows substantial promise as a potential therapeutic agent for liver-related conditions. However, further validation through in vitro and in vivo studies is necessary. Key insights from this study include:•Screening of flavanols and their derivatives to determine pharmacological and bioactive properties using ADMET, molinspiration, and pass prediction analysis.•Docking of shortlisted flavone derivatives with proteins having essential functions.•Analysis of the best protein-flavonoid docked complexes using molecular dynamics simulation to determine the flavonoid's efficiency and stability within a system.

Keywords: ADMET; Exploring the Effectiveness of Flavone Derivatives for Treating Liver Diseases: Utilizing DFT, Molecular Docking, and Molecular Dynamics Techniques; Flavone; Flavonoids DFT; MD simulation; Molecular docking; PASS.