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Second-generation 4,5,6,7-tetrahydrobenzo[d]thiazoles as novel DNA gyrase inhibitors.
Lamut, Andraz; Skok, Ziga; Barancoková, Michaela; Gutierrez, Lucas J; Cruz, Cristina D; Tammela, Päivi; Draskovits, Gábor; Szili, Petra Éva; Nyerges, Ákos; Pál, Csaba; Molek, Peter; Bratkovic, Tomaz; Ilas, Janez; Zidar, Nace; Zega, Anamarija; Enriz, Ricardo D; Kikelj, Danijel; Tomasic, Tihomir.
Afiliación
  • Lamut A; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Skok Z; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Barancoková M; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Gutierrez LJ; Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, IMIBIO-CONICET Chacabuco 915, San Luis, 5700, Argentina.
  • Cruz CD; Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki, FI-00014, Finland.
  • Tammela P; Drug Research Programme, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), Helsinki, FI-00014, Finland.
  • Draskovits G; Synthetic & Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
  • Szili PÉ; Synthetic & Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
  • Nyerges Á; DoctoralSchool of Multidisciplinary Medical Sciences, University of Szeged, Szeged, H-6726, Hungary.
  • Pál C; Synthetic & Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
  • Molek P; Synthetic & Systems Biology Unit, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, H-6726, Hungary.
  • Bratkovic T; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Ilas J; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Zidar N; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Zega A; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Enriz RD; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
  • Kikelj D; Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, IMIBIO-CONICET Chacabuco 915, San Luis, 5700, Argentina.
  • Tomasic T; Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, Ljubljana, 1000, Slovenia.
Future Med Chem ; 12(4): 277-297, 2020 02.
Article en En | MEDLINE | ID: mdl-32043377
ABSTRACT

Aim:

DNA gyrase and topoisomerase IV are essential bacterial enzymes, and in the fight against bacterial resistance, they are important targets for the development of novel antibacterial drugs.

Results:

Building from our first generation of 4,5,6,7-tetrahydrobenzo[d]thiazole-based DNA gyrase inhibitors, we designed and prepared an optimized series of analogs that show improved inhibition of DNA gyrase and topoisomerase IV from Staphylococcus aureus and Escherichia coli, with IC50 values in the nanomolar range. Importantly, these inhibitors also show improved antibacterial activity against Gram-positive strains.

Conclusion:

The most promising inhibitor, 29, is active against Enterococcus faecalis, Enterococcus faecium and S. aureus wild-type and resistant strains, with minimum inhibitory concentrations between 4 and 8 µg/ml, which represents good starting point for development of novel antibacterials.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Girasa de ADN / Benzotiazoles / Inhibidores de Topoisomerasa II / Bacterias Grampositivas / Antibacterianos Límite: Humans Idioma: En Revista: Future Med Chem Año: 2020 Tipo del documento: Article País de afiliación: Eslovenia

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Girasa de ADN / Benzotiazoles / Inhibidores de Topoisomerasa II / Bacterias Grampositivas / Antibacterianos Límite: Humans Idioma: En Revista: Future Med Chem Año: 2020 Tipo del documento: Article País de afiliación: Eslovenia