Open Access

Molecules

, том 27 , издание 16 , страницы 5085

Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome

Caroline W Karanja ¹

Nimishetti Naganna ¹

Nader S. Abutaleb ^{2, 3}

Neetu Dayal ¹

Kenneth I Onyedibe ^{1, 4}

Uma K. Aryal ^{2, 5}

Mohamed N. Seleem ^{2, 3}

Herman O. Sintim ^{1, 4, 6}

Скрыть аффилиации авторов Показать аффилиации авторов: 6 аффилиаций

Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA |

Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, 625 Harrison Street, West Lafayette, IN 47907, USA |

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd, Blacksburg, VA 24061, USA |

⁴

Purdue Institute of Inflammation, Immunology and Infectious Disease, West Lafayette, IN 47907, USA |

⁵

Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA |

⁶

Institute for Drug Discovery, Purdue University, 720 Clinic Drive, West Lafayette, IN 47907, USA |

Тип публикации: Journal Article

Дата публикации: 2022-08-10

MDPI

Molecules

scimago Q1

wos Q2

БС1

SJR: 0.865

CiteScore: 8.6

Impact factor: 4.6

ISSN: 14203049

DOI: 10.3390/molecules27165085

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PubMed ID: 36014324

Organic Chemistry

Drug Discovery

Physical and Theoretical Chemistry

Pharmaceutical Science

Molecular Medicine

Analytical Chemistry

Chemistry (miscellaneous)

Краткое описание

A new class of alkynyl isoquinoline antibacterial compounds, synthesized via Sonogashira coupling, with strong bactericidal activity against a plethora of Gram-positive bacteria including methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus) strains is presented. HSN584 and HSN739, representative compounds in this class, reduce methicillin-resistant S. aureus (MRSA) load in macrophages, whilst vancomycin, a drug of choice for MRSA infections, was unable to clear intracellular MRSA. Additionally, both HSN584 and HSN739 exhibited a low propensity to develop resistance. We utilized comparative global proteomics and macromolecule biosynthesis assays to gain insight into the alkynyl isoquinoline mechanism of action. Our preliminary data show that HSN584 perturb S. aureus cell wall and nucleic acid biosynthesis. The alkynyl isoquinoline moiety is a new scaffold for the development of potent antibacterial agents against fatal multidrug-resistant Gram-positive bacteria.

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European Journal of Medicinal Chemistry	European Journal of Medicinal Chemistry, 2, 12.5% European Journal of Medicinal Chemistry 2 публикации, 12.5%
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Results in Chemistry	Results in Chemistry, 1, 6.25% Results in Chemistry 1 публикация, 6.25%
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Karanja C. W. et al. Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome // Molecules. 2022. Vol. 27. No. 16. p. 5085.

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Karanja C. W., Naganna N., Abutaleb N. S., Dayal N., Onyedibe K. I., Aryal U. K., Seleem M. N., Sintim H. O. Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome // Molecules. 2022. Vol. 27. No. 16. p. 5085.

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TY - JOUR

DO - 10.3390/molecules27165085

UR - https://doi.org/10.3390/molecules27165085

TI - Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome

T2 - Molecules

AU - Karanja, Caroline W

AU - Naganna, Nimishetti

AU - Abutaleb, Nader S.

AU - Dayal, Neetu

AU - Onyedibe, Kenneth I

AU - Aryal, Uma K.

AU - Seleem, Mohamed N.

AU - Sintim, Herman O.

PY - 2022

DA - 2022/08/10

PB - MDPI

SP - 5085

IS - 16

VL - 27

PMID - 36014324

SN - 1420-3049

ER -

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@article{2022_Karanja,

author = {Caroline W Karanja and Nimishetti Naganna and Nader S. Abutaleb and Neetu Dayal and Kenneth I Onyedibe and Uma K. Aryal and Mohamed N. Seleem and Herman O. Sintim},

title = {Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome},

journal = {Molecules},

year = {2022},

volume = {27},

publisher = {MDPI},

month = {aug},

url = {https://doi.org/10.3390/molecules27165085},

number = {16},

pages = {5085},

doi = {10.3390/molecules27165085}

}

MLA

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Karanja, Caroline W., et al. “Isoquinoline Antimicrobial Agent: Activity against Intracellular Bacteria and Effect on Global Bacterial Proteome.” Molecules, vol. 27, no. 16, Aug. 2022, p. 5085. https://doi.org/10.3390/molecules27165085.

Издатель

MDPI

Журнал

Molecules

scimago Q1

wos Q2

БС1

SJR

0.865

CiteScore

8.6

Impact factor

4.6

ISSN

14203049 (Print, Electronic)