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 language | English |
|---|---|
| Pages (from-to) | 125-135 |
| Number of pages | 11 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 166 |
| DOIs | |
| Publication status | Published - 15 Mar 2019 |
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Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry
Cite this
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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
UR - http://www.scopus.com/inward/record.url?scp=85060535315&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2019.01.050
DO - 10.1016/j.ejmech.2019.01.050
M3 - Article
AN - SCOPUS:85060535315
VL - 166
SP - 125
EP - 135
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -