External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains

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External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains. / Шетнев, А.А.; Тарасенко, Марина; Котлярова, В.; Байков, Сергей Валентинович ; Гейль, Кирилл Константинович; Касаткина, Светлана Олеговна; Сибинчич, Николина ; Шаройко, Владимир Владимирович; Рогачева, Елизавета; Краева, Людмила Александровна.

In: Molecular Diversity, 31.05.2022.

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

BibTeX

@article{ae5ab1d8d2384a1db22ef91edb9d2bcf,

title = "External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains",

abstract = "A new route to 5-amino-1,2,4-thiadiazole derivatives via reaction of N-chloroamidines with isothiocyanates has been proposed. The advantages of this method are high product yields (up to 93%), the column chromatography-free workup procedure, scalability and the absence of additive oxidizing agents or transition metal catalysts. The 28 examples of 5-amino-1,2,4-thiadiazole derivatives obtaining via the proposing protocol were evaluated in vitro against ESKAPE pathogens strains (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae). It was found that compounds 5ba, 5bd, 6a, 6d and 6c have potent antibacterial activity (MIC values 0.09–1.5 μg mL −1), which is superior to the activity of commercial antibiotics such as pefloxacin (MIC 4–8 μg mL −1) and streptomycin (MIC 2–32 μg mL −1). The additional cytotoxic assay of hit compounds on PANC-1 cell line demonstrated the low or non-cytotoxicity activity at the same level of concentrations. Thus, these 5 compounds are promising starting point for further antimicrobial drug development. Graphical abstract: [Figure not available: see fulltext.]. ",

keywords = "Amidines, Antimicrobial, ESKAPE, Heterocycles, Isothiocyanates",

author = "А.А. Шетнев and Марина Тарасенко and В. Котлярова and Байков, {Сергей Валентинович} and Гейль, {Кирилл Константинович} and Касаткина, {Светлана Олеговна} and Николина Сибинчич and Шаройко, {Владимир Владимирович} and Елизавета Рогачева and Краева, {Людмила Александровна}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.",

year = "2022",

month = may,

day = "31",

doi = "10.1007/s11030-022-10445-1",

language = "English",

journal = "Molecular Diversity",

issn = "1381-1991",

publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains

AU - Шетнев, А.А.

AU - Тарасенко, Марина

AU - Котлярова, В.

AU - Байков, Сергей Валентинович

AU - Гейль, Кирилл Константинович

AU - Касаткина, Светлана Олеговна

AU - Сибинчич, Николина

AU - Шаройко, Владимир Владимирович

AU - Рогачева, Елизавета

AU - Краева, Людмила Александровна

PY - 2022/5/31

Y1 - 2022/5/31

N2 - A new route to 5-amino-1,2,4-thiadiazole derivatives via reaction of N-chloroamidines with isothiocyanates has been proposed. The advantages of this method are high product yields (up to 93%), the column chromatography-free workup procedure, scalability and the absence of additive oxidizing agents or transition metal catalysts. The 28 examples of 5-amino-1,2,4-thiadiazole derivatives obtaining via the proposing protocol were evaluated in vitro against ESKAPE pathogens strains (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae). It was found that compounds 5ba, 5bd, 6a, 6d and 6c have potent antibacterial activity (MIC values 0.09–1.5 μg mL −1), which is superior to the activity of commercial antibiotics such as pefloxacin (MIC 4–8 μg mL −1) and streptomycin (MIC 2–32 μg mL −1). The additional cytotoxic assay of hit compounds on PANC-1 cell line demonstrated the low or non-cytotoxicity activity at the same level of concentrations. Thus, these 5 compounds are promising starting point for further antimicrobial drug development. Graphical abstract: [Figure not available: see fulltext.].

AB - A new route to 5-amino-1,2,4-thiadiazole derivatives via reaction of N-chloroamidines with isothiocyanates has been proposed. The advantages of this method are high product yields (up to 93%), the column chromatography-free workup procedure, scalability and the absence of additive oxidizing agents or transition metal catalysts. The 28 examples of 5-amino-1,2,4-thiadiazole derivatives obtaining via the proposing protocol were evaluated in vitro against ESKAPE pathogens strains (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae). It was found that compounds 5ba, 5bd, 6a, 6d and 6c have potent antibacterial activity (MIC values 0.09–1.5 μg mL −1), which is superior to the activity of commercial antibiotics such as pefloxacin (MIC 4–8 μg mL −1) and streptomycin (MIC 2–32 μg mL −1). The additional cytotoxic assay of hit compounds on PANC-1 cell line demonstrated the low or non-cytotoxicity activity at the same level of concentrations. Thus, these 5 compounds are promising starting point for further antimicrobial drug development. Graphical abstract: [Figure not available: see fulltext.].

KW - Amidines

KW - Antimicrobial

KW - ESKAPE

KW - Heterocycles

KW - Isothiocyanates

UR - http://www.scopus.com/inward/record.url?scp=85131092707&partnerID=8YFLogxK

UR - https://link.springer.com/10.1007/s11030-022-10445-1

UR - https://www.mendeley.com/catalogue/23728593-f1db-3116-8b97-41256c511b9b/

U2 - 10.1007/s11030-022-10445-1

DO - 10.1007/s11030-022-10445-1

M3 - Article

JO - Molecular Diversity

JF - Molecular Diversity

SN - 1381-1991

ER -

ID: 95472388