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Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit : Synthesis and biological activity against the eskape panel of pathogens. / Chuprun, Sergey; Dar’in, Dmitry; Rogacheva, Elizaveta; Kraeva, Liudmila; Levin, Oleg; Manicheva, Olga; Dogonadze, Marine; Vinogradova, Tatiana; Bakulina, Olga; Krasavin, Mikhail.

In: Antibiotics, Vol. 9, No. 10, 666, 01.10.2020, p. 1-21.

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

Harvard

Chuprun, S, Dar’in, D, Rogacheva, E, Kraeva, L, Levin, O, Manicheva, O, Dogonadze, M, Vinogradova, T, Bakulina, O & Krasavin, M 2020, 'Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit: Synthesis and biological activity against the eskape panel of pathogens', Antibiotics, vol. 9, no. 10, 666, pp. 1-21. https://doi.org/10.3390/antibiotics9100666, https://doi.org/10.3390/antibiotics9100666

APA

Chuprun, S., Dar’in, D., Rogacheva, E., Kraeva, L., Levin, O., Manicheva, O., Dogonadze, M., Vinogradova, T., Bakulina, O., & Krasavin, M. (2020). Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit: Synthesis and biological activity against the eskape panel of pathogens. Antibiotics, 9(10), 1-21. [666]. https://doi.org/10.3390/antibiotics9100666, https://doi.org/10.3390/antibiotics9100666

Vancouver

Chuprun S, Dar’in D, Rogacheva E, Kraeva L, Levin O, Manicheva O et al. Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit: Synthesis and biological activity against the eskape panel of pathogens. Antibiotics. 2020 Oct 1;9(10):1-21. 666. https://doi.org/10.3390/antibiotics9100666, https://doi.org/10.3390/antibiotics9100666

Author

Chuprun, Sergey ; Dar’in, Dmitry ; Rogacheva, Elizaveta ; Kraeva, Liudmila ; Levin, Oleg ; Manicheva, Olga ; Dogonadze, Marine ; Vinogradova, Tatiana ; Bakulina, Olga ; Krasavin, Mikhail. / Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit : Synthesis and biological activity against the eskape panel of pathogens. In: Antibiotics. 2020 ; Vol. 9, No. 10. pp. 1-21.

BibTeX

@article{4c37407dd05f44748bd682b67bfe0072,
title = "Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit: Synthesis and biological activity against the eskape panel of pathogens",
abstract = "Starting from the structure of antimycobacterial screening hit OTB-021 which was devoid of activity against ESKAPE pathogens, we designed, synthesized and tested two mutually isomeric series of novel simplified analogs, 2-and 4-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, bearing various amino side chains. These compounds demonstrated a reverse bioactivity profile being inactive against M. tuberculosis while inhibiting the growth of all ESKAPE pathogens (with variable potency patterns) except for Gram-negative P. aeruginosa. Reduction potentials (E1/2, V) measured for selected compounds by cyclic voltammetry were tightly grouped in the −1.3–−1.1 V range for a reversible single-electron reduction. No apparent correlation between the E1/2 values and the ESKAPE minimum inhibitory concentrations was established, suggesting possible significance of other factors, besides the compounds{\textquoteright} reduction potential, which determine the observed antibacterial activity. Generally, more negative E1/2 values were displayed by 2-(3-nitro-1,2,4-triazol-1yl)pyrimidines, which is in line with the frequently observed activity loss on moving the 3-nitro1,2,4-triazol-1-yl moiety from position 4 to position 2 of the pyrimidine nucleus.",
keywords = "3-nitro-1,2,4-triazole, Antimycobacterial activity, Bioreducible prodrugs, Cyclic voltammetry, ESKAPE pathogens, Nitroazoles, Nucleophilic aromatic substitution, Reversible singleelectron reduction, MULTIDRUG-RESISTANT, bioreducible prodrugs, 4-triazole, MOIETY, antimycobacterial activity, 3-nitro-1, EFFICACIOUS IN-VITRO, NONTOXIC NITROFURANS, nitroazoles, reversible single-electron reduction, 2, cyclic voltammetry, DRUGS, nucleophilic aromatic substitution, NITRO, DERIVATIVES",
author = "Sergey Chuprun and Dmitry Dar{\textquoteright}in and Elizaveta Rogacheva and Liudmila Kraeva and Oleg Levin and Olga Manicheva and Marine Dogonadze and Tatiana Vinogradova and Olga Bakulina and Mikhail Krasavin",
note = "Funding Information: Funding: This research was supported by the Russian Federation Government Megagrant 14.W03.031.0025. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = oct,
day = "1",
doi = "10.3390/antibiotics9100666",
language = "English",
volume = "9",
pages = "1--21",
journal = "Antibiotics",
issn = "2079-6382",
publisher = "MDPI AG",
number = "10",

}

RIS

TY - JOUR

T1 - Mutually isomeric 2-and 4-(3-nitro-1,2,4-triazol-1yl)pyrimidines inspired by an antimycobacterial screening hit

T2 - Synthesis and biological activity against the eskape panel of pathogens

AU - Chuprun, Sergey

AU - Dar’in, Dmitry

AU - Rogacheva, Elizaveta

AU - Kraeva, Liudmila

AU - Levin, Oleg

AU - Manicheva, Olga

AU - Dogonadze, Marine

AU - Vinogradova, Tatiana

AU - Bakulina, Olga

AU - Krasavin, Mikhail

N1 - Funding Information: Funding: This research was supported by the Russian Federation Government Megagrant 14.W03.031.0025. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Starting from the structure of antimycobacterial screening hit OTB-021 which was devoid of activity against ESKAPE pathogens, we designed, synthesized and tested two mutually isomeric series of novel simplified analogs, 2-and 4-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, bearing various amino side chains. These compounds demonstrated a reverse bioactivity profile being inactive against M. tuberculosis while inhibiting the growth of all ESKAPE pathogens (with variable potency patterns) except for Gram-negative P. aeruginosa. Reduction potentials (E1/2, V) measured for selected compounds by cyclic voltammetry were tightly grouped in the −1.3–−1.1 V range for a reversible single-electron reduction. No apparent correlation between the E1/2 values and the ESKAPE minimum inhibitory concentrations was established, suggesting possible significance of other factors, besides the compounds’ reduction potential, which determine the observed antibacterial activity. Generally, more negative E1/2 values were displayed by 2-(3-nitro-1,2,4-triazol-1yl)pyrimidines, which is in line with the frequently observed activity loss on moving the 3-nitro1,2,4-triazol-1-yl moiety from position 4 to position 2 of the pyrimidine nucleus.

AB - Starting from the structure of antimycobacterial screening hit OTB-021 which was devoid of activity against ESKAPE pathogens, we designed, synthesized and tested two mutually isomeric series of novel simplified analogs, 2-and 4-(3-nitro-1,2,4-triazol-1-yl)pyrimidines, bearing various amino side chains. These compounds demonstrated a reverse bioactivity profile being inactive against M. tuberculosis while inhibiting the growth of all ESKAPE pathogens (with variable potency patterns) except for Gram-negative P. aeruginosa. Reduction potentials (E1/2, V) measured for selected compounds by cyclic voltammetry were tightly grouped in the −1.3–−1.1 V range for a reversible single-electron reduction. No apparent correlation between the E1/2 values and the ESKAPE minimum inhibitory concentrations was established, suggesting possible significance of other factors, besides the compounds’ reduction potential, which determine the observed antibacterial activity. Generally, more negative E1/2 values were displayed by 2-(3-nitro-1,2,4-triazol-1yl)pyrimidines, which is in line with the frequently observed activity loss on moving the 3-nitro1,2,4-triazol-1-yl moiety from position 4 to position 2 of the pyrimidine nucleus.

KW - 3-nitro-1,2,4-triazole

KW - Antimycobacterial activity

KW - Bioreducible prodrugs

KW - Cyclic voltammetry

KW - ESKAPE pathogens

KW - Nitroazoles

KW - Nucleophilic aromatic substitution

KW - Reversible singleelectron reduction

KW - MULTIDRUG-RESISTANT

KW - bioreducible prodrugs

KW - 4-triazole

KW - MOIETY

KW - antimycobacterial activity

KW - 3-nitro-1

KW - EFFICACIOUS IN-VITRO

KW - NONTOXIC NITROFURANS

KW - nitroazoles

KW - reversible single-electron reduction

KW - 2

KW - cyclic voltammetry

KW - DRUGS

KW - nucleophilic aromatic substitution

KW - NITRO

KW - DERIVATIVES

UR - http://www.scopus.com/inward/record.url?scp=85092018551&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/364331aa-2ca3-3e0a-b427-cbc78777cc2e/

U2 - 10.3390/antibiotics9100666

DO - 10.3390/antibiotics9100666

M3 - Article

AN - SCOPUS:85092018551

VL - 9

SP - 1

EP - 21

JO - Antibiotics

JF - Antibiotics

SN - 2079-6382

IS - 10

M1 - 666

ER -

ID: 69946287