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

Abstract

The growing global threat of multidrug-resistant (MDR) bacteria exposes the urgency of a 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 the development of efficient photosensitizers for PDI needs a change in paradigm.

This project sets the basis for that change, through the development of new families of antibacterial drugs, based on iron (II) complexes and efficient photosensitizers (with alternative action mechanisms) to implement an innovative therapeutic methodology to destroy MDR bacteria.

The novel photosensitizers, based on biocompatible cationic azo-templates, are expected to present strong light absorption above 550 nm (therapeutic window), long triplet lifetimes, and high quantum yields of ROS formation, photostability, and positive charge for targeting Gram-negative bacteria, low molecular weight and adequate partition coefficients to enhance their permeation into bacteria membranes.

In addition, iron (II) complexes with potential antibacterial activity, through Fenton-type ROS generation, will be developed in parallel.

The combination of the new photosensitizers with iron (II) complexes is expected to provide a synergic effect to obtain bimodal antibiotic drugs, leading to an innovative clinical methodology based on a dual therapy.

The evaluation of these innovative molecules in photodynamic inactivation of MDR bacteria will be performed in vitro, while structure-activity relationships will be established to further optimize the design/synthesis of the new chemical entities. In addition, specific irradiation devices will be devised for use with the optimized photosensitizers.

The main goal is the development of new antibacterial bimodal entities and an innovative dual phototherapy (DUALPDI) methodology for the treatment of superficial infections (burn and surgical wounds, periodontal disease), often caused by MDR bacteria.

1. SMALL CATIONIC ORTHO-5,15-DI-HETEROARYL-PORPHYRINS DERIVATIVES AND THEIR APPLICATIONS IN PHOTOINACTIVATION OF MICROORGANISMS, Maria M. Pereira, Luís G. Arnaut, Carolina S. Vinagreiro, Gabriela C.D.J. Silva, Kate C. Blanco, Vanderlei S. Bagnato, Natália M. Inada, Ped. P. Patente Nº 20191000032263
2.  Outreach activities

Casstelo Branco

Ciencia vica

Jogo