Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis

Mikhail Krasavin, Alexei Lukin, Tatiana Vedekhina, Olga Manicheva, Marine Dogonadze, Tatiana Vinogradova, Natalia Zabolotnykh, Elizaveta Rogacheva, Liudmila Kraeva, Vladimir Sharoyko, Tatiana B. Tennikova, Dmitry Dar'in, Evgeny Sokolovich

Research output

2 Citations (Scopus)

Abstract

A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 μM and displayed low toxicity when evaluated in mice.

Original languageEnglish
Pages (from-to)125-135
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume166
DOIs
Publication statusPublished - 15 Mar 2019

Fingerprint

Piperidines
Nitrofurans
Multidrug-Resistant Tuberculosis
Mycobacterium tuberculosis
Retinal Pigments
Cytotoxicity
Amides
Toxicity
Epithelial Cells
Cell Line
Pharmaceutical Preparations
In Vitro Techniques

Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

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title = "Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis",
abstract = "A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 μM and displayed low toxicity when evaluated in mice.",
keywords = "Acylation, Antimycobacterial, ARPE-19 cell line, ESKAPE panel, Multidrug resistance, Nitrofuran antimicrobials, Non-specific toxicity, Periphery optimization, Prins reaction, Spirocycles, Tuberculosis",
author = "Mikhail Krasavin and Alexei Lukin and Tatiana Vedekhina and Olga Manicheva and Marine Dogonadze and Tatiana Vinogradova and Natalia Zabolotnykh and Elizaveta Rogacheva and Liudmila Kraeva and Vladimir Sharoyko and Tennikova, {Tatiana B.} and Dmitry Dar'in and Evgeny Sokolovich",
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day = "15",
doi = "10.1016/j.ejmech.2019.01.050",
language = "English",
volume = "166",
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journal = "European Journal of Medicinal Chemistry",
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Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis. / Krasavin, Mikhail; Lukin, Alexei; Vedekhina, Tatiana; Manicheva, Olga; Dogonadze, Marine; Vinogradova, Tatiana; Zabolotnykh, Natalia; Rogacheva, Elizaveta; Kraeva, Liudmila; Sharoyko, Vladimir; Tennikova, Tatiana B.; Dar'in, Dmitry; Sokolovich, Evgeny.

In: European Journal of Medicinal Chemistry, Vol. 166, 15.03.2019, p. 125-135.

Research output

TY - JOUR

T1 - Attachment of a 5-nitrofuroyl moiety to spirocyclic piperidines produces non-toxic nitrofurans that are efficacious in vitro against multidrug-resistant Mycobacterium tuberculosis

AU - Krasavin, Mikhail

AU - Lukin, Alexei

AU - Vedekhina, Tatiana

AU - Manicheva, Olga

AU - Dogonadze, Marine

AU - Vinogradova, Tatiana

AU - Zabolotnykh, Natalia

AU - Rogacheva, Elizaveta

AU - Kraeva, Liudmila

AU - Sharoyko, Vladimir

AU - Tennikova, Tatiana B.

AU - Dar'in, Dmitry

AU - Sokolovich, Evgeny

PY - 2019/3/15

Y1 - 2019/3/15

N2 - A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 μM and displayed low toxicity when evaluated in mice.

AB - A selectively antimycobacterial compound belonging to the nitrofuran class of antimicrobials has been developed via conjugation of the nitrofuran moiety to a series of spirocyclic piperidines through an amide linkage. It proved to have comparable activity against drug-sensitive (H37Rv) strain as well as multidrug-resistant, patient-derived strains of Mycobacterium tuberculosis. The compound is druglike, showed no appreciable cytotoxicity toward human retinal pigment epithelial cell line ARPE-19 in concentrations up to 100 μM and displayed low toxicity when evaluated in mice.

KW - Acylation

KW - Antimycobacterial

KW - ARPE-19 cell line

KW - ESKAPE panel

KW - Multidrug resistance

KW - Nitrofuran antimicrobials

KW - Non-specific toxicity

KW - Periphery optimization

KW - Prins reaction

KW - Spirocycles

KW - Tuberculosis

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M3 - Article

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