Sulfonamides complexed with metals as mycobacterial biofilms inhibitors.

Rapidly growing mycobacteria (RGM) are found in non-sterile water and often associated with severe post-surgical infections and affect immunocompromised patients. In addition, RGM can prevent the host's immune response and have the ability to adhere to and form biofilms on biological and synthetic substrates, making pharmacological treatment difficult because conventional antimicrobials are ineffective against biofilms. Thus, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this context, sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against various microorganisms. Considering the importance of combating RGM-associated infections, this study aimed to evaluate the activity of sulfonamide metal complexes against RGM biofilm. The sulfonamides were tested individually for their ability to inhibit mycobacterial formation and destroy the preformed biofilm of standard RGM strains, such as Mycobacterium abscessus, M. fortuitum, and M. massiliense. All sulfonamides complexed with metals could reduce, at subinhibitory concentrations, the adhesion and biofilm formation of three RGM species in polystyrene tubes. It is plausible that the anti-biofilm capacity of the compounds is due to the inhibition of c-di-GMP synthesis, which is an important signal for RGM biofilm formation. Hence, the impacts and scientific contribution of this study are based on the discovery of a potential new therapeutic option against RGM-associated biofilm infections. Sulfonamides complexed with metals have proven to be a useful and promising tool to reduce microbial adhesion on inert surfaces, stimulating the improvement of methodologies to insert compounds as new antibacterial and coating agents for medical and hospital materials.

Identification of antimicrobial activity among new sulfonamide metal complexes for combating rapidly growing mycobacteria.

Mycobacteriosis is a type of infection caused by rapidly growing mycobacteria (RGM), which can vary from localized illness, such as skin disease, to disseminated disease. Amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem and sulfamethoxazole are antimicrobial drugs chosen to treat such illnesses; however, not all patients obtain the cure. The reason why the treatment does not work for those patients is related to the fact that some clinical strains present resistance to the existing antimicrobial drugs; thereby, the research of new therapeutic approaches is extremely relevant. The coordination of antimicrobial drugs to metals is a promising alternative in the development of effective compounds against resistant microorganisms. Sulfonamides complexed with Au, Cd, Ag, Cu, and Hg have shown excellent activity against a variety of microorganisms. Considering the importance of fighting against infections associated with RGM, the objective of this study is to evaluate the antimycobacterial activity of metal complexes of sulfonamides against RGM. Complexed sulfonamides activity were individually tested and in association with trimethoprim. The minimum inhibitory concentration (MIC) and time-kill curve of compounds against the standard strains of RGM [Mycobacterium abscessus (ATCC 19977), Mycobacterium fortuitum (ATCC 6841) and Mycobacterium massiliense (ATCC 48898)] was determined. The interaction of sulfonamides with trimethoprim was defined by inhibitory concentration index fractional for each association. The results showed that sulfonamides complexed whit metals have outstanding antimicrobial activity when compared to free sulfamethoxazole, bactericidal activity and synergistic effect when combined with trimethoprim.