ABSTRACT
Antibiotic resistance associated with pulmonary infection agents has become a public health problem, being considered one of the main priorities for immediate resolution. Thus, to increase the therapeutic options in the fight against resistant microorganisms, the synthesis of molecules from pre-existing drugs has shown to be a promising alternative. In this sense, the present work reports the synthesis, characterization, and biological evaluation (against fungal and bacterial agents that cause lung infections) of potential metallodrugs based on sulfamethoxazole complexed with AuI, AgI, HgII, CdII, NiII, and CuII. The minimal inhibitory concentration (MIC) value was used to evaluate the antifungal and antibacterial properties of the compounds. In addition, it was also evaluated the antibiofilm capacity in Pseudomonas aeruginosa, through the quantification of its biomass and visualization using atomic force microscopy. For each case, molecular docking calculations were carried out to suggest the possible biological target of the assayed inorganic complexes. Our results indicated that the novel inorganic complexes are better antibacterial and antifungal than the commercial antibiotic sulfamethoxazole, highlighting the AgI-complex, which was able to inhibit the growth of microorganisms that cause lung diseases with concentrations in the 2-8 µg mL-1 range, probably at targeting dihydropteroate synthetase - a key enzyme involved in the folate synthesis. Furthermore, sulfamethoxazole complexes were able to inhibit the formation of bacterial biofilms at significantly lower concentrations than free sulfamethoxazole, probably mainly targeting the active site of LysR-type transcriptional regulator (PqsR). Overall, the present study reports preliminary results that demonstrate the derivatization of sulfamethoxazole with transition metal cations to obtain potential metallodrugs with applications as antimicrobial and antifungal against pulmonary infections, being an alternative for drug-resistant strains.
Subject(s)
Antifungal Agents , Sulfamethoxazole , Sulfamethoxazole/pharmacology , Antifungal Agents/pharmacology , Molecular Docking Simulation , Anti-Bacterial Agents/chemistry , Biofilms , Microbial Sensitivity Tests , Pseudomonas aeruginosaABSTRACT
The antibacterial activity of sulfadiazine Au-PPh3, sulfadiazine Ph2P-Au-Au-PPh2, sulfamethoxazole Au-PPh3, sulfamethoxazole Ph2P-Au-Au-PPh2, sulfamethoxazole Au-PPh3 were tested against Pseudomonas aeruginosa. The antibacterial activity of sulfonamide was tested against P. aeruginosa through the MIC assay, quantitative analysis of biofilm inhibition and observation of biofilm formation with fluorescence microscopy. Besides, the compounds presented remarkable inhibition of P. aeruginosa biofilm formation. Furthermore, molecular docking was performed to identify the key structural features of these compounds with the binding site of the LasR receptor.
Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Gold/pharmacology , Pseudomonas aeruginosa/drug effects , Sulfonamides/pharmacology , Anti-Bacterial Agents/chemistry , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Gold/chemistry , Microbial Sensitivity Tests , Microscopy, Fluorescence , Molecular Docking Simulation , Protein Binding , Pseudomonas aeruginosa/physiology , Sulfonamides/chemistry , Trans-Activators/chemistry , Trans-Activators/metabolismABSTRACT
The drug-resistant strains of Staphylococcus aureus have been considered as one of the serious health threats, which are related to high patient hospitalization rates. Besides, Staphylococcus aureus biofilm formation exhibits a drug-tolerant nature and shows nonspecific resistance against a broad-spectrum of antibiotics. The emergence of drug-resistant bacteria stimulated the development of novel medicines as a strategy to control infections. In this study, we evaluated the antibacterial and anti-biofilm activity of gold-complexed sulfonamides against Staphylococcus aureus strains such as methicillin-resistant S. aureus and clinical isolates. Our data showed that the exposure of gold-complexed sulfonamides promoted a remarkable reduction in the bacterial adhesion. Also, confocal microscopy displayed the effects of the compounds on in the bacterial cell biofilm, revealed that the compounds decreased the biofilm formation. Our results also demonstrated that gold-complexed sulfonamides exhibited potent antibacterial activity against Staphylococcus aureus strains. Besides, all compounds presented a synergic antibacterial activity when were associated with classical antibiotics. Gold-complexed sulfonamide compounds did not promote toxic effects on Caenorhabditis elegans. Thus, our results showed that the coordination of sulfonamide with gold is a promising alternative in the development of safe and active compounds against methicillin-resistant and clinical isolates S. aureus.
Subject(s)
Biofilms/drug effects , Gold/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Sulfonamides/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Adhesion/drug effects , Brazil , Caenorhabditis elegans/drug effects , Drug Synergism , Gold/chemistry , Humans , Methicillin Resistance/drug effects , Microbial Sensitivity Tests , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Sulfonamides/chemistry , Toxicity TestsABSTRACT
The title compound, [Au(C(10)H(9)N(4)O(2)S)(C(18)H(15)P)], is nearly linear at Au(I), with Au-N = 2.0707 (18) A, Au-P = 2.2310 (8) A and N-Au-P 171.93 (5) degrees. The molecules are linked by intermolecular N-H...O bonds.
