Antimicrobial activity of hydralazine against methicillin-resistant and methicillin-susceptible Staphylococcus aureus.

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 µg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.

Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.

Antifungal activity of cisatracurium against fluconazole-resistant Candida isolates and its antibiofilm effects.

Aim: To evaluate the antifungal activity of cisatracurium against Candida spp. resistant to fluconazole strains in planktonic and biofilm forms, in addition to determining its mechanism of action. Materials & methods: Antifungal activity and pharmacological interactions were determined using broth microdilution methods and the mechanism of action was evaluated by flow cytometry and molecular docking. Results: Cisatracurium presented antifungal activity against Candida spp. planktonic cells due to alterations of mitochondrial transmembrane potential leading to cellular apoptosis in addition to interacting with important targets related to cellular respiration, membrane and cell wall evidenced by molecular docking. Furthermore, the drug both prevented biofilm formation and impaired mature biofilms. Conclusion: Cisatracurium exhibits potential antifungal activity against Candida spp.

Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells.

Objective: To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against Candida spp. and the action mechanism. Methods: We used broth microdilution assays to determine the MIC, checkerboard assays to investigate synergism, and flow cytometry and molecular docking tests to ascertain action mechanism. Results: Hydralazine alone had antifungal activity in the range of 16-128 µg/ml and synergistic effect with itraconazole versus 100% of the fungal isolates, while there was synergy with fluconazole against 11.11% of the isolates. There was molecular interaction with the receptors exo-B(1,3)-glucanase and CYP51, causing reduced cell viability and DNA damage. Conclusion: Hydralazine is synergistic with itraconazole and triggers cell death of Candida spp. at low concentrations, demonstrating antifungal potential.

Synergistic activity of diclofenac sodium with oxacillin against planktonic cells and biofilm of methicillin-resistant Staphylococcus aureus strains.

Aim: To evaluate the activity of diclofenac sodium and synergism with oxacillin against clinical strains of SARM in plactonic cells, antibiofilm and biofilm. Materials & methods: Synergism activity was assessed using the fractional inhibitory concentration index and its possible mechanism of action by flow cytometry. Results: The synergistic activity of diclofenac sodium with oxacillin was observed against plactonic cells, antibiofilm and in biofilm formed from clinical methicillin-resistant Staphylococcus aureus strains. Conclusion: This combination caused damage to the integrity of the membrane and ruptures in the DNA of the cells, leading to apoptosis.