Design, synthesis and antibacterial study of new potent and selective coumarin–chalcone derivatives for the treatment of tenacibaculosis

• Published in: Bioorganic & medicinal chemistry Vol. 23; no. 21; pp. 7045 - 7052
• Main Authors: Vazquez-Rodriguez, Saleta, Lama López, Raquel, Matos, Maria João, Armesto-Quintas, Gabriel, Serra, Silvia, Uriarte, Eugenio, Santana, Lourdes, Borges, Fernanda, Muñoz Crego, Angeles, Santos, Ysabel
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.11.2015; Elsevier
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Aquaculture; Biochemistry & Molecular Biology; Chalcone; Chalcone - chemistry; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Coumarin; Coumarins - chemistry; Drug Design; Escherichia coli - drug effects; Fish Diseases - microbiology; Fish Diseases - prevention & control; Fishes; Flavobacteriaceae Infections - microbiology; Flavobacteriaceae Infections - prevention & control; Flavobacteriaceae Infections - veterinary; Humans; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Pharmacology & Pharmacy; Physical Sciences; Pseudomonas aeruginosa - drug effects; Science & Technology; Staphylococcus aureus - drug effects; Tenacibaculum - drug effects; Tenacibaculum - isolation & purification; Tenacibaculum maritimum; Antibacterial; Coumarin; Tenacibaculum maritimum; Chalcone; Aquaculture; BACTERIA; ANTIOXIDANT; FLEXIBACTER-MARITIMUS; DOVER SOLE
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2015.09.028

[Display omitted] With the aim of finding new chemical entities selective for fish pathogens to avoid drug resistance in humans, a series of coumarin–chalcone hybrid compounds with different patterns of substitution were designed and synthesized. Their antibacterial activity was evaluated against important types of human bacteria strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and against a fourteen strains of the marine pathogen Tenacibaculum maritimum, responsible for tenacibaculosis in fish, which is an important disease that causes great economical loss in the aquaculture industry. All the amino derivatives 5–12 presented high activity against different strains of T. maritimum, no activity against any of the three human pathogenic bacteria strains and no toxicity. Compounds 6, 7 and 11 were the most promising molecules. The most sensitive strains to these compounds were LL01 8.3.8 and LL01 8.3.1, being compound 11 up to 20 times more active than enrofloxacin. Therefore these scaffolds are good candidates for aquaculture treatments, avoiding possible drug resistance problems in humans.