%A Reetesh  Kumar
%A Yogesh Srivastava
%A Somnath Maji
%A Seemab Siddiqui
%A Rajeev Kumar Tyagi
%A Pandiyan  Muthuramalingam
%A Sunil Kumar Singh
%A Savitri Tiwari
%A Geetika Verma
%A Daniela Paula de Toledo Thomazella
%A Hyunsuk  Shin
%A Dinesh Kumar Prajapati
%A Pankaj Kumar  Rai
%A Samir Kumar  Beura 
%A Abhishek Ramachandra  Panigrahi
%A Fabio Rogerio de  Moraes 
%A Pasupuleti Visweswara  Rao 
%O The copyright of this article belongs to Springer Link 
%J Nucleus India
%T In silico evaluation of natural compounds to confirm their anti-DNA gyrase activity

%X The slow clearance of bacteria owing to drug resistance to the currently available antibiotics has been a global public health issue. The development of antibiotic resistance in Staphylococcus aureus has become prevalent in community-acquired infections, posing a significant challenge. DNA gyrase, an enzyme essential in all bacteria but absent in higher eukaryotes, emerges as an attractive target for novel antibacterial agents. This type II topoisomerase introduces negative supercoils in double-stranded DNA, at the expense of ATP, during DNA replication. In this study, we conducted a comprehensive screening of natural compound libraries from the ZINC database using different computational approaches targeting DNA gyrase activity. We identified five promising compounds following a detailed screening of drug-like compounds using pharmacokinetic-based studies, including the determination of the compound absorption, distribution, metabolism, excretion, and toxicity. Furthermore, based on protein?ligand docking studies, we showed the position, orientation, and binding affinity of the selected compounds within the active site of DNA gyrase. Overall, our study provides a primary reference to explore the molecular mechanisms associated with the antibacterial activity of the selected compounds, representing an important step toward the discovery of novel DNA gyrase inhibitors. Further investigation involving structural optimization as well as comprehensive in vivo and in vitro evaluations are necessary to fully explore the potential of these chemicals as effective antibacterial agents.


%K ADMET; Antibiotic resistance; DNA Gyrase; Staphylococcus aureus; Zinc database
%P 167-182
%V 66
%D 2023
%R https://doi.org/10.1007/s13237-023-00426-6
%I SPRINGER LINK
%L open3188