TY  - JOUR
N1  - The copyright of this article belongs to Springer Link 
ID  - open3188
UR  - https://link.springer.com/article/10.1007/s13237-023-00426-6
A1  - Kumar, Reetesh 
A1  - Srivastava, Yogesh
A1  - Maji, Somnath
A1  - Siddiqui, Seemab
A1  - Tyagi, Rajeev Kumar
A1  - Muthuramalingam, Pandiyan 
A1  - Singh, Sunil Kumar
A1  - Tiwari, Savitri
A1  - Verma, Geetika
A1  - Thomazella, Daniela Paula de Toledo
A1  - Shin, Hyunsuk 
A1  - Prajapati, Dinesh Kumar
A1  - Rai, Pankaj Kumar 
A1  - Beura , Samir Kumar 
A1  - Panigrahi, Abhishek Ramachandra 
A1  - Moraes , Fabio Rogerio de 
A1  - Rao , Pasupuleti Visweswara 
Y1  - 2023/06/03/
N2  - 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.


PB  - SPRINGER LINK
JF  - Nucleus India
VL  - 66
KW  - ADMET; Antibiotic resistance; DNA Gyrase; Staphylococcus aureus; Zinc database
TI  - In silico evaluation of natural compounds to confirm their anti-DNA gyrase activity

SP  - 167
EP  - 182
ER  -