Journal of Medicinal Chemistry, volume 60, issue 16, pages 7108-7122

Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery

Azzali Elisa ¹

Machado Diana ²

Kaushik Amit Kant ^{3, 4}

Vacondio Federica ⁵

Flisi Sara ⁶

Cabassi Clotilde Silvia ⁶

Lamichhane Gyanu ^{3, 4}

Viveiros Miguel ²

Costantino Gabriele ⁵

Pieroni Marco ⁵

Hide authors affiliations Show authors affiliations: 6 affiliations

Centro Interdipartimentale Misure (CIM) ‘G. Casnati’, University of Parma, Parco Area delle Scienze 23/A, 43124 Parma, Italy |

Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira, 100, 1349-008 Lisbon, Portugal |

Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, 1503 East Jefferson Street, Baltimore, Maryland 21231-1002, United States |

⁴

Taskforce to Study Resistance Emergence & Antimicrobial development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, United States |

⁵

University of Parma |

⁶

Department of Veterinary Science, University of Parma, via del Taglio 10, 43126 Parma, Italy |

Publication type: Journal Article

Publication date: 2017-08-10

American Chemical Society (ACS)

Journal: Journal of Medicinal Chemistry

Quartile SCImago

Quartile WOS

Impact factor: 7.3

ISSN: 00222623, 15204804

DOI: 10.1021/acs.jmedchem.7b00793

Copy DOI

Drug Discovery

Molecular Medicine

Abstract

Tuberculosis remains one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extremely drug-resistant strains is a significant reason for concern. This makes the discovery of novel antitubercular agents a cogent priority. We have previously addressed this need by reporting a series of substituted 2-aminothiazoles capable to inhibit the growth of actively replicating, nonreplicating persistent, and resistant Mycobacterium tuberculosis strains. Clues from the structure-activity relationships lining up the antitubercular activity were exploited for the rational design of improved analogues. Two compounds, namely N-phenyl-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 7a and N-(pyridin-2-yl)-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 8a, were found to show high inhibitory activity toward susceptible M. tuberculosis strains, with an MIC90 of 0.125-0.25 μg/mL (0.33-0.66 μM) and 0.06-0.125 μg/mL (0.16-0.32 μM), respectively. Moreover, they maintained good activity also toward resistant strains, and they were selective over other bacterial species and eukaryotic cells, metabolically stable, and apparently not susceptible to the action of efflux pumps.

By date By citations

Citations by journals

	1 2 3 4 5 6
European Journal of Medicinal Chemistry	European Journal of Medicinal Chemistry, 6, 10% European Journal of Medicinal Chemistry 6 publications, 10%
Molecules	Molecules, 2, 3.33% Molecules 2 publications, 3.33%
Polycyclic Aromatic Compounds	Polycyclic Aromatic Compounds, 2, 3.33% Polycyclic Aromatic Compounds 2 publications, 3.33%
Pharmaceuticals	Pharmaceuticals, 2, 3.33% Pharmaceuticals 2 publications, 3.33%
Medicinal Chemistry Research	Medicinal Chemistry Research, 2, 3.33% Medicinal Chemistry Research 2 publications, 3.33%
Journal of Molecular Structure	Journal of Molecular Structure, 2, 3.33% Journal of Molecular Structure 2 publications, 3.33%
Journal of Saudi Chemical Society	Journal of Saudi Chemical Society, 2, 3.33% Journal of Saudi Chemical Society 2 publications, 3.33%
Bioorganic and Medicinal Chemistry Letters	Bioorganic and Medicinal Chemistry Letters, 2, 3.33% Bioorganic and Medicinal Chemistry Letters 2 publications, 3.33%
Bioorganic Chemistry	Bioorganic Chemistry, 2, 3.33% Bioorganic Chemistry 2 publications, 3.33%
Journal of Organic Chemistry	Journal of Organic Chemistry, 2, 3.33% Journal of Organic Chemistry 2 publications, 3.33%
RSC Advances	RSC Advances, 2, 3.33% RSC Advances 2 publications, 3.33%
Journal of Antibiotics	Journal of Antibiotics, 1, 1.67% Journal of Antibiotics 1 publication, 1.67%
Combinatorial Chemistry and High Throughput Screening	Combinatorial Chemistry and High Throughput Screening, 1, 1.67% Combinatorial Chemistry and High Throughput Screening 1 publication, 1.67%
Archiv der Pharmazie	Archiv der Pharmazie, 1, 1.67% Archiv der Pharmazie 1 publication, 1.67%
Journal of Medicinal Chemistry	Journal of Medicinal Chemistry, 1, 1.67% Journal of Medicinal Chemistry 1 publication, 1.67%
Organic and Biomolecular Chemistry	Organic and Biomolecular Chemistry, 1, 1.67% Organic and Biomolecular Chemistry 1 publication, 1.67%
Anti-Infective Agents	Anti-Infective Agents, 1, 1.67% Anti-Infective Agents 1 publication, 1.67%
Mini-Reviews in Organic Chemistry	Mini-Reviews in Organic Chemistry, 1, 1.67% Mini-Reviews in Organic Chemistry 1 publication, 1.67%
Future Medicinal Chemistry	Future Medicinal Chemistry, 1, 1.67% Future Medicinal Chemistry 1 publication, 1.67%
Frontiers in Microbiology	Frontiers in Microbiology, 1, 1.67% Frontiers in Microbiology 1 publication, 1.67%
Nature Reviews Chemistry	Nature Reviews Chemistry, 1, 1.67% Nature Reviews Chemistry 1 publication, 1.67%
Molecular Diversity	Molecular Diversity, 1, 1.67% Molecular Diversity 1 publication, 1.67%
BMC Chemistry	BMC Chemistry, 1, 1.67% BMC Chemistry 1 publication, 1.67%
Organic Letters	Organic Letters, 1, 1.67% Organic Letters 1 publication, 1.67%
Tetrahedron	Tetrahedron, 1, 1.67% Tetrahedron 1 publication, 1.67%
Bioorganic and Medicinal Chemistry	Bioorganic and Medicinal Chemistry, 1, 1.67% Bioorganic and Medicinal Chemistry 1 publication, 1.67%
ChemMedChem	ChemMedChem, 1, 1.67% ChemMedChem 1 publication, 1.67%
Asian Journal of Organic Chemistry	Asian Journal of Organic Chemistry, 1, 1.67% Asian Journal of Organic Chemistry 1 publication, 1.67%
Advanced Synthesis and Catalysis	Advanced Synthesis and Catalysis, 1, 1.67% Advanced Synthesis and Catalysis 1 publication, 1.67%
	1 2 3 4 5 6

Citations by publishers

	2 4 6 8 10 12 14 16 18
Elsevier	Elsevier, 17, 28.33% Elsevier 17 publications, 28.33%
Springer Nature	Springer Nature, 6, 10% Springer Nature 6 publications, 10%
Wiley	Wiley, 6, 10% Wiley 6 publications, 10%
American Chemical Society (ACS)	American Chemical Society (ACS), 6, 10% American Chemical Society (ACS) 6 publications, 10%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 5, 8.33% Royal Society of Chemistry (RSC) 5 publications, 8.33%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 4, 6.67% Multidisciplinary Digital Publishing Institute (MDPI) 4 publications, 6.67%
Taylor & Francis	Taylor & Francis, 4, 6.67% Taylor & Francis 4 publications, 6.67%
Bentham Science	Bentham Science, 3, 5% Bentham Science 3 publications, 5%
Pleiades Publishing	Pleiades Publishing, 3, 5% Pleiades Publishing 3 publications, 5%
King Saud University	King Saud University, 2, 3.33% King Saud University 2 publications, 3.33%
Future Medicine	Future Medicine, 1, 1.67% Future Medicine 1 publication, 1.67%
Frontiers Media S.A.	Frontiers Media S.A., 1, 1.67% Frontiers Media S.A. 1 publication, 1.67%
	2 4 6 8 10 12 14 16 18

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Azzali E. et al. Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery // Journal of Medicinal Chemistry. 2017. Vol. 60. No. 16. pp. 7108-7122.

GOST all authors (up to 50) Copy

Azzali E., Machado D., Kaushik A. K., Vacondio F., Flisi S., Cabassi C. S., Lamichhane G., Viveiros M., Costantino G., Pieroni M. Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery // Journal of Medicinal Chemistry. 2017. Vol. 60. No. 16. pp. 7108-7122.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1021/acs.jmedchem.7b00793

UR - https://doi.org/10.1021%2Facs.jmedchem.7b00793

TI - Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery

T2 - Journal of Medicinal Chemistry

AU - Costantino, Gabriele

AU - Azzali, Elisa

AU - Pieroni, Marco

AU - Machado, Diana

AU - Kaushik, Amit Kant

AU - Vacondio, Federica

AU - Flisi, Sara

AU - Cabassi, Clotilde Silvia

AU - Lamichhane, Gyanu

AU - Viveiros, Miguel

PY - 2017

DA - 2017/08/10 00:00:00

PB - American Chemical Society (ACS)

SP - 7108-7122

IS - 16

VL - 60

SN - 0022-2623

SN - 1520-4804

ER -

BibTex |

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@article{2017_Azzali,

author = {Gabriele Costantino and Elisa Azzali and Marco Pieroni and Diana Machado and Amit Kant Kaushik and Federica Vacondio and Sara Flisi and Clotilde Silvia Cabassi and Gyanu Lamichhane and Miguel Viveiros},

title = {Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery},

journal = {Journal of Medicinal Chemistry},

year = {2017},

volume = {60},

publisher = {American Chemical Society (ACS)},

month = {aug},

url = {https://doi.org/10.1021%2Facs.jmedchem.7b00793},

number = {16},

pages = {7108--7122},

doi = {10.1021/acs.jmedchem.7b00793}

}

MLA

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MLA Copy

Azzali, Elisa, et al. “Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery.” Journal of Medicinal Chemistry, vol. 60, no. 16, Aug. 2017, pp. 7108-7122. https://doi.org/10.1021%2Facs.jmedchem.7b00793.

Found error?

Publisher

American Chemical Society (ACS)

Journal

Journal of Medicinal Chemistry

Quartile SCImago

Quartile WOS

Impact factor

7.3

ISSN

00222623 (Print)
15204804 (Electronic)