Preparation of analogues of natural products combined with silver nanoparticles and their application against resistant bacteria Mycobacterium abscessus

• Grant number: 21/07971-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): November 01, 2022
• Effective date (End): April 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: João Henrique Ghilardi Lago
• Grantee: Larissa Verena Figueiredo de Oliveira
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated scholarship(s): 23/16143-7 - Assessing the Microbicidal Efficacy of Natural Product Analogues Combined with Silver Nanoparticles against WHO Priority Resistant Bacteria, BE.EP.PD

Abstract

There has been a considerable increase in infections by multidrug-resistant microorganisms in the last few years both due to the natural adaptability of these microorganisms to the known antibiotics and especially due to the misuse and overuse of them. Along with that, the current Covid-19 pandemic in which there has been a high rate of antibiotic utilization in patients even with a relatively low rate of co- or secondary infection. Therefore, collateral damage to the current status of the pandemic could be a significant increase in the number of drug-resistant bacteria, which worsens the situation that was already problematic. Natural compounds have shown great bactericidal potential, even against some multidrug-resistant strains and they already have been studied as alternatives to current drugs. These compounds can be used as found in natura or they can be used as prototypes for designing new molecules with improved pharmacological potential. However, in general, they have low bioavailability which greatly impairs their therapeutic use. So, an alternative to overcome this problem is the combination of these natural compounds with nanoparticles in order to improve their bioavailability and microbicidal capacity. Silver nanoparticles (AgNP) are excellent candidates to be used in combination with natural products due to their intrinsic microbicidal potential and they do not confer resistance to their use. Thus the main goal of this project is to prepare analogues of the natural product gibbilimbol, which already showed considerable biological activity, combine them with silver nanoparticles and evaluate their microbicidal capacity against the resistant bacteria Mycobacterium abscessus. They are nontuberculous mycobacteria that cause serious infections, especially pulmonary infections that mainly affect immunocompromised people. Due to the increase in the number of cases of Mycobacterium abscessus infections and the limited therapeutic options for its treatment due to its resistance to multiple antibiotics, the search for alternative treatment methods against these microorganisms is necessary and urgent. (AU)