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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1360745
This article is part of the Research Topic Discovery of Small Molecule Lead Compounds: a Driving Force to Unravel New Anti-Cancer Targets and Mechanisms - Volume II View all 5 articles

Identification of Anti-colorectal cancer inhibitors using Resveratrol derivatives: Molecular docking, dynamic simulation, and DFT calculation

Provisionally accepted
Shopnil Akash Shopnil Akash 1*Md R. Islam Md R. Islam 1Abdul A. Bhuiyan Abdul A. Bhuiyan 2Mirza N. Islam Mirza N. Islam 3Imren Bayil Imren Bayil 4Rasha M. Saleem Rasha M. Saleem 5Ghadeer M. Albadrani Ghadeer M. Albadrani 6Muath Alghadi Muath Alghadi 7Mohamed M. Abdel-Daim Mohamed M. Abdel-Daim 8
  • 1 Daffodil International University, Dhaka, Bangladesh
  • 2 Pabna University of Science & Technology, Pabna, Rajshahi, Bangladesh
  • 3 University of Rajshahi, Rajshahi, Rajshahi, Bangladesh
  • 4 University of Gaziantep, Gaziantep, Gaziantep, Türkiye
  • 5 Al Baha University, Al Bahah, Saudi Arabia
  • 6 Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
  • 7 King Saud University, Riyadh, Riyadh, Saudi Arabia
  • 8 Batterjee Medical College, Jeddah, Saudi Arabia

The final, formatted version of the article will be published soon.

    Colorectal cancer is the second leading cause of cancer-related deaths. In 2018, there were an esti-mated 1.8 million cases, and this number is projected to increase to 2.2 million by 2030. Despite its prevalence, the current therapeutic option has a lot of side effects and limitations. Therefore, this study was designed to employ a computational approach for the identification of anti-cancer inhib-itors against colorectal cancer using Resveratrol derivatives. Initially, the pass prediction spectrum of 50 derivatives was conducted and selected top seven compounds based on the maximum pass pre-diction score. After that, a comprehensive analysis, including Lipinski Rule, pharmacokinetics, ADMET profile study, molecular orbitals analysis, molecular docking, molecular dynamic simula-tions, and MM-PBSA binding free energy calculations. The reported binding affinity ranges of Resveratrol derivatives from molecular docking were -6.1 kcal/mol to -7.9 kcal/mol against the tar-geted receptor of human armadillo repeats domain of APC (PDB ID: 3NMW). Specifically, our findings reported that two compounds [(03) Resveratrol 3-beta-mono-D-glucoside, and (29) Resveratrol 3-Glucoside] displayed the highest level of effectiveness compared to all other deriva-tives (-7.7 kcal/mol and -7.9 kcal/mol), and favorable drug-likeness, and exceptional safety profiles. Importantly, almost all the molecules were reported as free from toxic effects. Subsequently, mo-lecular dynamic simulations conducted over 100ns confirmed the stability of the top two lig-and-protein complexes. These findings suggest that Resveratrol derivatives may be effective drug candidate to manage the colorectal cancer. However, further experimental research, such as in vitro/in vivo studies, is essential to validate these computational findings and confirm their practical value.

    Keywords: drug design, Resveratrol derivatives, colorectal cancer, molecular docking, Molecular Dynamics Simulation

    Received: 24 Dec 2023; Accepted: 25 Mar 2024.

    Copyright: © 2024 Akash, Islam, Bhuiyan, Islam, Bayil, Saleem, Albadrani, Alghadi and Abdel-Daim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shopnil Akash, Daffodil International University, Dhaka, Bangladesh

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.