An in silico molecular docking, ADMET and molecular dynamics simulations studies of azolyl-2H-chroman-4-ones as potential inhibitors against pathogenic fungi and bacteria

Abstract

Antimicrobial resistance is a major global threat. In an attempt to discover new compounds with improved efficiency and to overcome drug resistance, a library of 3960 compounds was designed as conformationally rigid analogues of oxiconazole with 2H-chroman-4-one, azole and substituted phenyl fragments. The antifungal and antibacterial activity of the compounds was evaluated using molecular docking studies in the active site of six fungal and four bacterial proteins to establish the binding affinity of the designed ligands. In-silico ADME and Lipinski’s rule were used to establish the drug-likeness properties of the compounds. This study revealed that all the designed compounds had a high binding affinity with the target proteins and formed H-bond and π-π interactions. The identified hits have been subjected to molecular dynamics simulations to study protein-ligand complex stability. This study has led to the identification of important compounds that can be developed further as therapeutic agents against pathogenic fungi and bacteria.

Communicated by Ramaswamy H. Sarma

HIGHLIGHTS

• Virtual screening of a library of 3960 2H-chroman-4-one derivatives against pathogenic fungi and bacteria

• Screened via molecular docking, ADME and Lipinski filter

• Bind to the active site of the protein target with good binding affinity

• MD simulation shows stability of the protein-ligand complex of identified hits

Keywords:

• Molecular docking
• ADME
• molecular dynamics
• antibacterial
• antifungal
• chromanones

Acknowledgements

The authors would like to acknowledge the founder Chancellor of the Institute, Bhagawan Sri Sathya Sai Baba for his guidance. We especially acknowledge the computational facility at Central Research Laboratory (CRL) – SSSIHL and Department of Chemistry, SSSIHL-ATP. MC thanks Sri Sathya Sai Institute of Higher Learning for the Institute fellowship.

Authors’ contributions

KVS Mani Chandrika: data curation, formal analysis, investigation, methodology, Writing-original draft. V Prathyusha: conceptualization, project administration, supervision, validation, visualization, writing-review and editing.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.