In silico evaluation of usnic acid derivatives to discover potential antibacterial drugs against DNA gyrase B and DNA topoisomerase IV

Abstract

Due to the rising increase in infectious diseases brought on by bacteria and anti-bacterial drug resistance, antibacterial therapy has become difficult. The majority of first-line antibiotics are no longer effective against numerous germs, posing a new hazard to global human health in the 21st century. Through the drug-likeness screening, 184 usnic acid derivatives were selected from an in-house database of 340 usnic acid compounds. The pharmacokinetics (ADMET) prediction produced fifteen hit compounds, of which the lead molecule was subsequently obtained through a molecular docking investigation. The lead compounds, labelled compound-277 and compound-276, respectively, with the substantial binding affinity towards the enzymes were obtained through further docking simulation on the DNA gyrase and DNA topoisomerase proteins. Additionally, molecular dynamic (MD) simulation was performed for 300 ns on the lead compounds in order to confirm the stability of the docked complexes and the binding pose discovered during docking tests. Due to their intriguing pharmacological characteristics, these substances may be promising therapeutic candidate for anti-bacterial medication.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anti-bacterial
• docking
• MD simulation
• usnic acid

Authors’ contributions

MR and ARI data acquisition, experimental and manuscript drafting, SF Data acquisition and experimental. MESS critical review, SNT review and fund acquisition. AKMMH and MFFMA conceptualization, design and supervision.

Disclosure statement

The authors have no conflict of interest.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The authors would like to thank the Lembaga Koko Malaysia (Malaysian Cocoa Board) for supporting our work by awarding the grant (University reference number: RDU 210710) to Universiti Malaysia Pahang.