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

Abstract

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.

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

“…The cadmium complexes were less toxic, with the most active species (X = SCN) showing a MIC of 25 µg/mL against P. aeruginosa. In 2016, Agertt et al evaluated sulfonamide metal complexes of Au, Ag, Cd, Cu and Hg for their antimycobacterial activities against M. abscessus, M. fortuitum and M. massiliense [191]. Cadmium and mercury complexes showed MICs of 4.9 µg/mL against M. fortuitum and M. massiliense and of 19.5 and 9.8 µg/mL, respectively, against M. abscessus.…”

Revisiting Therapeutic Sulfonamides in the Attempt to Improve the Antimicrobial Properties Through Metal-Ion Coordination

“…In contrast, the ternary Cu(II) complexes associating sulfathiazole and a series of cephalosporins (cefazolin, cefalotin, cefotaxime and ceftriaxone) reported by Anacona et al did not prove to be characterized by the same synergetic effect; their antibacterial activity was comparable to that of the free cephalosporin [3]. The antibacterial activity of ternary complexes of Ag(I) and Au(I) with sulfonamides and phosphine derivatives, respectively (Table I), was reported with interesting results [1,2,[33][34][35]. The study of the Au(I) monomer complex and Ag(I) polymeric complex with sulfamethoxazole reported by Marques et al concluded that these complexes exhibited significant antibacterial properties against E. coli, S. aureus and P. aeruginosa.…”

Gold Drugs with {Au(PPh3)}+ Moiety: Advantages and Medicinal Applications

“…Compound 37 and 38 ( Figure 6) in a different study were also assessed for their activity and synergistic activity with trimethoprim in different species of Mycobacterium (M. abscessus, M. forticum and M. massiliense) responsible for nosocomial infections that are typically not transmitted human to human but rather from the environment. [68] Significant improvement in activity was observed upon conjugation to a {Au(PPh 3 )} + center and synergy between 37 or 38 and trimethoprim was observed in most cases with these Mycobacterium species. In our laboratory, complex 52 ( Figure 8) with known TB drug pyrazinamide as an N donor ligand was first screened for its activity towards M. smegmatis (MIC = 60 μM) and had a higher activity than the control drug isoniazid.…”

“…The synergy between trimethoprim and 51 was also observed with M. tuberculosis providing promising results for future studies. Compound 37 and 38 (Figure 6) in a different study were also assessed for their activity and synergistic activity with trimethoprim in different species of Mycobacterium ( M. abscessus, M. forticum and M. massiliense) responsible for nosocomial infections that are typically not transmitted human to human but rather from the environment [68] . Significant improvement in activity was observed upon conjugation to a {Au(PPh 3 )} + center and synergy between 37 or 38 and trimethoprim was observed in most cases with these Mycobacterium species.…”