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 -