Ligand-Based Design of Novel Quinoline Derivatives as Potential Anticancer Agents: An In-Silico Virtual Screening Approach

Khaoula Mkhayar, Ossama Daoui, Rachid Haloui, Kaouakeb Elkhattabi, Abdelmoula Elabbouchi, Samir Chtita, Abdelouahid Samadi, Souad Elkhattabi

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, using the Comparative Molecular Field Analysis (CoMFA) approach, the structure-activity relationship of 33 small quinoline-based compounds with biological anti-gastric cancer activity in vitro was analyzed in 3D space. Once the 3D geometric and energy structure of the target chemical library has been optimized and their steric and electrostatic molecular field descriptions computed, the ideal 3D-QSAR model is generated and matched using the Partial Least Squares regression (PLS) algorithm. The accuracy, statistical precision, and predictive power of the developed 3D-QSAR model were confirmed by a range of internal and external validations, which were interpreted by robust correlation coefficients ((Formula presented.) ; (Formula presented.) ; (Formula presented.)). After carefully analyzing the contour maps produced by the trained 3D-QSAR model, it was discovered that certain structural characteristics are beneficial for enhancing the anti-gastric cancer properties of Quinoline derivatives. Based on this information, a total of five new quinoline compounds were developed, with their biological activity improved and their drug-like bioavailability measured using POM calculations. To further explore the potential of these compounds, molecular docking and molecular dynamics simulations were performed in an aqueous environment for 100 nanoseconds, specifically targeting serine/threonine protein kinase. Overall, the new findings of this study can serve as a starting point for further experiments with a view to the identification and design of a potential next-generation drug for target therapy against cancer.

Original languageEnglish
Article number426
JournalMolecules
Volume29
Issue number2
DOIs
Publication statusPublished - Jan 2024

Keywords

  • 3D-QSAR
  • ADME-Tox
  • CoMFA
  • MM-GBSA
  • POM
  • anti-gastric cancer
  • molecular docking
  • molecular dynamics
  • quinoline

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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