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

Title: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

Volume: 17 Issue: 4

Author(s): Divya Chauhan*, Sushil Kumar, Syed Riaz Hashim and Vinit Raj

Affiliation:

• Department of Chemistry, School of Sciences, IFTM University, Moradabad, Uttar Pradesh,India

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

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.

Cite this article as:

Chauhan Divya *, Kumar Sushil , Hashim Riaz Syed and Raj Vinit , 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, Current Computer-Aided Drug Design 2021; 17(4) . https://dx.doi.org/10.2174/1573409916666200525150410