6533b855fe1ef96bd12b1438
RESEARCH PRODUCT
2,6-Disubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives as potent staphylococcal biofilm inhibitors.
Elisa GiovannettiElisa GiovannettiBarbara ParrinoMaria Grazia CusimanoVeronica Di SarnoGirolamo CirrincionePatrizia DianaGiovanna Li PetriStella CascioferroDomenico SchillaciSimona Musellasubject
Indoles3Anti-virulence agentStaphylococcus1-b][1Bacterial growthAnti-Biofilm agentsmedicine.disease_causeSettore BIO/19 - Microbiologia GeneraleGram-Positive Bacteriaimidazo[201 natural sciencesVirulence factorMicrobiology03 medical and health sciencesStaphylococcus epidermidisDrug DiscoveryGram-Negative BacteriaThiadiazolesmedicineStaphylococcal biofilm inhibitorsEscherichia coli030304 developmental biologyPharmacology0303 health sciences4]thiadiazole derivativesbiologyStaphylococcal biofilm inhibitorVirulenceAnti-Biofilm agents; Anti-virulence agents; imidazo[21-b][134]thiadiazole derivatives; Staphylococcal biofilm inhibitors; Anti-Bacterial Agents; Biofilms; Gram-Negative Bacteria; Gram-Positive Bacteria; Indoles; Staphylococcus; Thiadiazoles; Virulence010405 organic chemistryPseudomonas aeruginosaChemistryimidazo[21-b][134]thiadiazole derivativesOrganic ChemistryBiofilmGeneral Medicinebiology.organism_classificationSettore CHIM/08 - Chimica FarmaceuticaAnti-Biofilm agent0104 chemical sciencesAnti-Bacterial AgentsAnti-virulence agentsStaphylococcus aureusBiofilms1 3 4 thiadiazole derivativesdescription
Abstract A class of 36 new 2-(6-phenylimidazo[2,-1-b][1,3,4]thiadiazol-2-yl)-1H-indoles was efficiently synthesized and evaluated for their anti-biofilm properties against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 25923, S. aureus ATCC 6538 and Staphylococcus epidermidis ATCC 12228, and the Gram-negative strains Pseudomonas aeruginosa ATCC 15442 and Escherichia coli ATCC 25922. Many of these new compounds, were able to inhibit biofilm formation of the tested staphylococcal strains showing BIC50 lower than 10 μg/ml. In particular, derivatives 9c and 9h showed remarkable anti-biofilm activity against S. aureus ATCC 25923 with BIC50 values of 0.5 and 0.8 μg/ml, respectively, whereas compound 9aa was the most potent against S. aureus ATCC 6538, with a BIC50 of 0.3 μg/ml. Remarkably, these compounds showed effects in the early stages of the biofilm formation without affecting the mature biofilm of the same strains and the viability of the planktonic form. Their ability in counteracting a virulence factor (biofilm formation) without interfering with the bacterial growth in the free life form make them novel valuable anti-virulence agents.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-04-01 | European journal of medicinal chemistry |