Antimicrobial Activity of Substituted Benzopentathiepin-6-amines. / Khomenko, Tatyana M.; Korchagina, Dina V.; Baev, Dmitry S. et al.
In: Journal of Antibiotics, Vol. 72, No. 8, 01.08.2019, p. 590-599.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Antimicrobial Activity of Substituted Benzopentathiepin-6-amines
AU - Khomenko, Tatyana M.
AU - Korchagina, Dina V.
AU - Baev, Dmitry S.
AU - Vassiliev, Pavel M.
AU - Volcho, Konstantin P.
AU - Salakhutdinov, Nariman F.
N1 - Publisher Copyright: © 2019, The Author(s), under exclusive licence to the Japan Antibiotics Research Association.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - A number of substituted benzopentathiepin-6-amines and their analogues without a polysulfur ring were synthesized and evaluated in vitro for antimicrobial activity against a panel of reference bacterial and fungal strains. Trifluoroacetamide 14 demonstrated high antibacterial activity against Staphylococcus aureus (MRSA strain) with a MIC of 4 μg/mL, which was four-fold higher than the activity of a reference drug amoxicillin. This compound was also most active against the Candida albicans fungus (MIC of 1 μg ml−1), whereas amide 17 containing a morpholine substituent was most active against the Cryptococcus neoformans fungus (MIC of 2 μg ml−1). These compounds have no hemolytic activity and are low cytotoxic. Replacement of the pentathiepine ring with 1,3-dithiolan-2-one or 1,3-dithiolane moieties leads to loss of antimicrobial activity. Based on the QSAR analysis and molecular docking data, bacterial DNA ligase might be one of the targets for the antibacterial activity of substituted benzopentathiepin-6-amines against S. aureus.
AB - A number of substituted benzopentathiepin-6-amines and their analogues without a polysulfur ring were synthesized and evaluated in vitro for antimicrobial activity against a panel of reference bacterial and fungal strains. Trifluoroacetamide 14 demonstrated high antibacterial activity against Staphylococcus aureus (MRSA strain) with a MIC of 4 μg/mL, which was four-fold higher than the activity of a reference drug amoxicillin. This compound was also most active against the Candida albicans fungus (MIC of 1 μg ml−1), whereas amide 17 containing a morpholine substituent was most active against the Cryptococcus neoformans fungus (MIC of 2 μg ml−1). These compounds have no hemolytic activity and are low cytotoxic. Replacement of the pentathiepine ring with 1,3-dithiolan-2-one or 1,3-dithiolane moieties leads to loss of antimicrobial activity. Based on the QSAR analysis and molecular docking data, bacterial DNA ligase might be one of the targets for the antibacterial activity of substituted benzopentathiepin-6-amines against S. aureus.
KW - DNA-LIGASE INHIBITORS
KW - BIOLOGICAL EVALUATION
KW - NATURAL-PRODUCTS
KW - DRUG DISCOVERY
KW - IN-VITRO
KW - VARACIN
KW - 8-(TRIFLUOROMETHYL)-1,2,3,4,5-BENZOPENTATHIEPIN-6-AMINE
KW - ANALOGS
KW - DESIGN
UR - http://www.scopus.com/inward/record.url?scp=85066239790&partnerID=8YFLogxK
U2 - 10.1038/s41429-019-0191-y
DO - 10.1038/s41429-019-0191-y
M3 - Article
C2 - 31118480
AN - SCOPUS:85066239790
VL - 72
SP - 590
EP - 599
JO - Journal of Antibiotics
JF - Journal of Antibiotics
SN - 0021-8820
IS - 8
ER -
ID: 20342462