Pharmacophore Generation, Quantitative Structure-Activity Relationship (QSAR), and Molecular Dynamic Simulation of Newly Substituted N-(6- Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)-2-(4-chloro-phenoxy)-acetamide for Anticancer Activity

Abstract

Objective: The main objective of the study was to develop the Quantitative Structure- Activity Relationship (QSAR) and pharmacophore model by using data obtained from HT-29 cells to develop potent lead molecule for the scientific community.

Materials and methods: Common pharmacophore model, atom-based 3D-QSAR, and molecular dynamic (MD) simulation were carried out via computational techniques by using 4H-chromene derivatives.

Results: The reliable common pharmacophoric hypothesis, DHH13 was generated and 3.95 survival value was also found. Furthermore, the statistically significant 3D-QSAR model was developed where r²=0.52 was found by using the Partial least squares (PLS) regression method. Phase predicted activity and Log GI⁵⁰ demonstrated an important atomic position in the structure of ligands to ascertain anti colon cancer activity. Also, MD simulation was carried out between top rank leads targeting IL-6 that provided better binding conformational and complex stability into the active pocket site of the target throughout the MD simulation.

Conclusion: The outcome of this design shows that the pharmacophore model and 3D-QSAR might be helpful for researchers in the field of medicinal chemistry to design and develop potential anti colon cancer compounds.

Keywords: 3D-QSAR model; 4H-Chromene; IL-6; colorectal cancer; molecular dynamic simulation.; pharmacophore.