Development of Novel Indole and Coumarin Derivatives as Antibacterial Agents That Target Histidine Kinase in S. aureus

Development of Novel Indole and Coumarin Derivatives as Antibacterial Agents That Target Histidine Kinase in S. aureus Full article

Journal

Applied Microbiology
ISSN: 2673-8007

Output data

Year: 2023, Volume: 3, Number: 4, Pages: 1214-1228 Pages count : 15 DOI: 10.3390/applmicrobiol3040084

Authors

Poonacha Lisha K. ¹ , Ramesh Rashmi ² , Ravish Akshay ³ , Mohan Arunkumar ³ , Uppar Pradeep M. ³ , Metri Prashant K. ³ , Shivananju Nanjunda Swamy ⁴ , Gaonkar Santosh L. ⁵ , Gopal Shubha ² , Sukhorukov Alexey Yu ⁶ , Pandey Vijay ^7,8,9 , Shubha Priya Babu ¹ , Basappa Basappa ³

Affiliations

1	Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India
2	Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore 570006, India
3	Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India
4	Department of Biotechnology, Technical Institutions Campus, Sri Jayachamarajendra College of Engineering, Jagadguru Sri Shivarathreeshwara University, Mysore 570006, India
5	Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal 576104, India
6	N.D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, Moscow 119991, Russia
7	Shenzhen Bay Laboratory, Shenzhen 518055, China
8	Tsinghua Berkeley Shenzhen Institute, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
9	Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China

Heterocyclic compounds can specifically regulate bacterial development by targeting specific bacterial enzymes and metabolic pathways. The ESKAPE pathogens are multidrug-resistant and cause nosocomial infections, which is one of the greatest challenges in clinical practice. The search for novel agents to combat resistant bacteria has become one of the most important areas of antibacterial research today. Heterocyclic compounds offer a valuable strategy in the fight against resistance as they can be designed to interact with bacterial targets that are less prone to developing resistance mechanisms. Bacterial histidine kinases (HKs), which are a component of two-component bacterial systems, are a promising target for new antibacterial compounds. We have designed and synthesized novel indole derivatives as antibacterial agents. Among the series, indole-coumarin (4b) and bisindole (4e) have shown the best inhibitory activity against S. aureus. Further, in silico docking studies show that compounds 4b and 4e could target histidine kinases in bacteria.

Poonacha L.K. , Ramesh R. , Ravish A. , Mohan A. , Uppar P.M. , Metri P.K. , Shivananju N.S. , Gaonkar S.L. , Gopal S. , Sukhorukov A.Y. , Pandey V. , Shubha P.B. , Basappa B.
Development of Novel Indole and Coumarin Derivatives as Antibacterial Agents That Target Histidine Kinase in S. aureus
Applied Microbiology. 2023. V.3. N4. P.1214-1228. DOI: 10.3390/applmicrobiol3040084 OpenAlex

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