Synthesis of bimodal molecules for photodynamic inactivation of resistant bacteria by dual therapy

• Grant number: 18/07961-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2018
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Radiology and Photobiology
• Agreement: Fundação para a Ciência e a Tecnologia (FCT)
• Principal Investigator: Vanderlei Salvador Bagnato
• Grantee: Vanderlei Salvador Bagnato
• Principal researcher abroad: Maria Miguens Pereira
• Institution abroad: Universidade de Coimbra (UC), Portugal
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated researchers: Cristina Kurachi ; Lilian Tan Moriyama ; Natalia Mayumi Inada

Abstract

The growing global threat of multidrug-resistant (MDR) bacteria exposes the urgency ofa new pipeline of efficient antimicrobial drugs, involving different mechanisms of action.Photodynamic inactivation (PDI) of bacteria, involving reactive oxygen species (ROS),is considered an alternative to classic antibiotics, but further progresses in thedevelopment of efficient photosensitizers for PDI needs a change in paradigm. Thisproject sets the basis for that change, through the development of new families ofantibacterial drugs, based on iron(II) complexes and efficient photosensitizers (withalternative action mechanisms) to implement an innovative therapeutic methodology todestroy MDR bacteria. The novel photosensitizers, based on biocompatible cationic azo-templates, are expected to present strong light absorption above 550 nm (therapeuticwindow), long triplet lifetimes, high quantum yields of ROS formation, photostability,positive charge for targeting Gram-negative bacteria, low molecular weight and adequatepartition coefficients to enhance their permeation into bacteria membranes. In addition,iron(II)complexes with potential antibacterial activity, through Fenton-type ROSgeneration, will be developed in parallel. The combination of the new photosensitizerswith iron(II)complexes is expected to provide a synergic effect to obtain bimodalantibiotic drugs, leading to an innovative clinical methdolology based on a dual therapy.The evaluation of these innovative molecules in photodynamic inactivation of MDRbacteria will be performed in vitro, while structure-activity relationships will beestablished to further optimize the design/synthesis of the new chemical entities. Inaddition, specific irradiation devices will be devised for use with the optimizedphotosensitizers. The main goal is the development of new antibacterial bimodal entitiesand an innovative dual phototherapy (DUALPDI) methodology for the treatment ofsuperficial infections (burn and surgical wounds, periodontal disease), often caused byMDR bacteria. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

AROSO, RAFAEL T.; DIAS, LUCAS D.; BLANCO, KATE C.; SOARES, JENNIFER M.; ALVES, FERNANDA; DA SILVA, GABRIELA J.; ARNAUT, LUIS G.; BAGNATO, VANDERLEI S.; PEREIRA, MARIETTE M.. Synergic dual phototherapy: Cationic imidazolyl photosensitizers and ciprofloxacin for eradication of in vitro and in vivo E. coli infections. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 233, p. 11-pg., 2022-06-09. (14/50857-8, 18/07961-0, 19/13569-8, 13/07276-1)