A novel scaffold to fightPseudomonas aeruginosapyocyanin production: early steps to novel antivirulence drugs

Author(s)

Froes, Thamires Quadros ^[1] ; Guido, Rafael V. C. ^[2] ; Metwally, Kamel ^[3] ; Castilho, Marcelo Santos ^{[4, 1]}

Affiliation

^[1] Univ Estadual Feira de Santana, Programa Posgrad Biotecnol, BR-44036900 Novo Horizonte, BA - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13563120 Sao Paulo - Brazil

^[3] Zagazig Univ, Fac Pharm, Dept Med Chem, Zagazig 44519 - Egypt

^[4] Univ Fed Bahia, Fac Farm, BR-40170115 Salvador, BA - Brazil

• Document type: Journal article
• Source: Future Medicinal Chemistry; v. 12, n. 16 AUG 2020.
• Web of Science Citations: 0

Abstract

Aim:Although the bacterial resistance is a growing concern worldwide, the development of antibacterial drugs has been steadily decreasing. One alternative to fight this issue relies on reducing the bacteria virulence without killing it. PhzS plays a pivotal role in pyocyanin production inPseudomonas aeruginosa.Results: A total of 31 thiazolidinedione derivatives were evaluated as putative PhzS inhibitors, using thermo shift assays. Compounds that significantly shifted PhzS's Tm had their mode of inhibition (cofactor competitor) and affinity calculated by thermo shift assays as well. The most promising compound (E)-5-(4-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)methoxy)benzylidene )thiazolidine-2,4-dione had their affinity confirmed by microscale thermophoresis (K-d = 18 mu M). Cellular assays suggest this compound reduces pyocyanin productionin vitro, but does not affectP. aeruginosaviability.Conclusion:The first inhibitor of PhzS is described. (AU)

• FAPESP's process: 16/13884-2 - Multi-User Equipment approved in grant 2013/07600-3: MicroScale Thermophoresis (MST)
• Grantee: Glaucius Oliva
• Support Opportunities: Multi-user Equipment Program