Marina Gjorgjieva (Avtor), Tihomir Tomašić (Avtor), Michaela Barančokova (Avtor), Sotirios Katsamakas (Avtor), Janez Ilaš (Avtor), Päivi Tammela (Avtor), Lucija Peterlin-Mašič (Avtor), Danijel Kikelj (Avtor)

Povzetek

Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and are validated targets for antibacterial drug discovery. Starting from our recently reported 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-based DNA gyrase B inhibitors, we replaced their central core with benzothiazole-2,6-diamine scaffold and interchanged substituents in positions 2 and 6. This resulted in equipotent nanomolar inhibitors of DNA gyrase from Escherichia coli displaying improved inhibition of Staphylococcus aureus DNA gyrase and topoisomerase IV from both bacteria. Compound 27 was the most balanced inhibitor of DNA gyrase and topoisomerase IV both from E. coli and S. aureus. The crystal structure of the 2-((2-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzothiazol-6-yl)amino)-2-oxoacetic acid (24) in complex with E. coli DNA gyrase B revealed the binding mode of the inhibitor in the ATP-binding pocket. Only some compounds possessed weak antibacterial activity against Gram-positive bacteria. These results provide a basis for structure-based optimization towards dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

Ključne besede

bioanorganska kemija;koordinacijske spojine;organorutenijevi kompleksi;diketonati;citotoksičnost;protirakava zdravila;organoruthenium complexes;diketonates;anticancer drugs;ROS;cytotoxicity;cell cycle arrest;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 543:542:615
COBISS: 4145265 Povezava se bo odprla v novem oknu
ISSN: 0022-2623
Št. ogledov: 898
Št. prenosov: 890
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: bioanorganska kemija;koordinacijske spojine;organorutenijevi kompleksi;diketonati;citotoksičnost;protirakava zdravila;
Konec prepovedi (OpenAIRE): 2017-08-19
Strani: str. 8941-8954
Letnik: ǂVol. ǂ59
Zvezek: ǂiss. ǂ19
Čas izdaje: 2016
DOI: 10.1021/acs.jmedchem.6b00864
ID: 11129697