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

Lisha K. Poonacha; Rashmi Ramesh; Akshay Ravish; Arunkumar Mohan; Pradeep M. Uppar; Prashant K. Metri; Nanjunda Swamy Shivananju; Santosh L. Gaonkar; Shubha Gopal; Alexey Yu Sukhorukov; Vijay Pandey; Priya Babu Shubha; Basappa Basappa

doi:10.3390/applmicrobiol3040084

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

Lisha K. Poonacha, Rashmi Ramesh, Akshay Ravish, Arunkumar Mohan, Pradeep M. Uppar, Prashant K. Metri, Nanjunda Swamy Shivananju, Santosh L. Gaonkar, Shubha Gopal, Alexey Yu Sukhorukov, Vijay Pandey^*, Priya Babu Shubha^*, Basappa Basappa^*

^*Corresponding author for this work

Department of Chemistry, Manipal Institute of Technology, Manipal

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1214-1228
Number of pages	15
Journal	Applied Microbiology
Volume	3
Issue number	4
DOIs	https://doi.org/10.3390/applmicrobiol3040084
Publication status	Published - 12-2023

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology (miscellaneous)
Chemical Engineering (miscellaneous)
Applied Microbiology and Biotechnology

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10.3390/applmicrobiol3040084

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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. (2023). Development of Novel Indole and Coumarin Derivatives as Antibacterial Agents That Target Histidine Kinase in S. aureus. Applied Microbiology, 3(4), 1214-1228. https://doi.org/10.3390/applmicrobiol3040084

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

abstract = "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.",

author = "Poonacha, \{Lisha K.\} and Rashmi Ramesh and Akshay Ravish and Arunkumar Mohan and Uppar, \{Pradeep M.\} and Metri, \{Prashant K.\} and Shivananju, \{Nanjunda Swamy\} and Gaonkar, \{Santosh L.\} and Shubha Gopal and Sukhorukov, \{Alexey Yu\} and Vijay Pandey and Shubha, \{Priya Babu\} and Basappa Basappa",

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doi = "10.3390/applmicrobiol3040084",

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Poonacha, LK, Ramesh, R, Ravish, A, Mohan, A, Uppar, PM, Metri, PK, Shivananju, NS, Gaonkar, SL, Gopal, S, Sukhorukov, AY, Pandey, V, Shubha, PB & Basappa, B 2023, 'Development of Novel Indole and Coumarin Derivatives as Antibacterial Agents That Target Histidine Kinase in S. aureus', Applied Microbiology, vol. 3, no. 4, pp. 1214-1228. https://doi.org/10.3390/applmicrobiol3040084

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T1 - Development of Novel Indole and Coumarin Derivatives as Antibacterial Agents That Target Histidine Kinase in S. aureus

AU - Poonacha, Lisha K.

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AU - Ravish, Akshay

AU - Mohan, Arunkumar

AU - Uppar, Pradeep M.

AU - Metri, Prashant K.

AU - Shivananju, Nanjunda Swamy

AU - Gaonkar, Santosh L.

AU - Gopal, Shubha

AU - Sukhorukov, Alexey Yu

AU - Pandey, Vijay

AU - Shubha, Priya Babu

AU - Basappa, Basappa

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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

Abstract

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