ABSTRACT
Candida ranks as among the most frequently encountered fungal infections that associated with high morbidity and mortality. Quinoxaline derivatives are a group of small molecules that showed a promising antimicrobial activity. This study aimed to investigate the fungicidal effects of 3-hydrazinoquinoxaline-2-thiol against Candida in comparison with Amphotericin B in vitro as a reference. Also, we aim to assess the efficacy of 3-hydrazinoquinoxaline-2-thiol in vivo using mice oral candidiasis model. Fifty-six Candida isolates were subjected to susceptibility testing by broth microdilution method for 3-hydrazinoquinoxaline-2-thiol and Amphotericin B. Therefore, Minimal inhibitory concentrations (MIC) were assessed and compared. The oral candidiasis mice model was used to evaluate the activity of 3-hydrazinoquinoxaline-2-thiol in vivo. Microbiological evaluation of progression and ELISA were used in this study. 3-hydrazinoquinoxaline-2-thiol was more effective than Amphotericin B against most clinical isolates of Candida albicans. Higher effectiveness was seen against Candida glabrata and Candida parapsilosis isolates. However, the efficiency against Candida tropicalis isolates varies. 3-hydrazinoquinoxaline-2-thiol was also effective against Pichia kudriavzevii and Clavispora lusitaniae. 3-hydrazinoquinoxaline-2-thiol showed a good efficacy in mice model against C. albicans cells ATCC 10231. 3-hydrazinoquinoxaline-2-thiol has shown promising antifungal and anti-inflammatory activity against different Candida species. More tests and experiments are needed.
ABSTRACT
Background: The growing resistance seen in various antibiotics, including those considered as last-resort options, underscores the pressing need for novel approaches and new substances to address MRSA infections. Combining antibiotics as a treatment approach can enhance effectiveness, expand the range of targeted bacteria, and minimize the likelihood of resistance emergence. This approach holds promise in addressing the escalating issue of antibiotic resistance. Purpose: This study seeks to investigate the potential synergy between 3-hydrazinoquinoxaline-2-thiol and penicillin against a diverse array of MRSA isolates, thereby providing insights into their combined antimicrobial action. Methods: Twenty-two clinical MRSA isolates subjected to broth microdilution to determine the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and penicillin. Subsequently, a checkerboard assay was employed to evaluate the interaction between 3-hydrazinoquinoxaline-2-thiol and penicillin, focusing on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of penicillin and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical MRSA strains. Penicillin exhibited MICs within a range of 1024 to 128 µg/mL, while 3-hydrazinoquinoxaline-2-thiol displayed MICs varying from 64 to 8 µg/mL. Remarkably, the combination of 3-hydrazinoquinoxaline-2-thiol and penicillin yielded a synergistic effect, resulting in a significant reduction of MICs by up to 64-fold. Conclusion: The potential of 3-hydrazinoquinoxaline-2-thiol in combination with penicillin as a viable solution against MRSA appears promising. However, to establish its practical utility, further extensive testing and experiments are essential.
ABSTRACT
Background: While the frequency of methicillin-resistant Staphylococcus aureus (MRSA) continues to rise globally, there is a fear regarding an increase in vancomycin resistance among S. aureus strains. As far back as the 1960s, MRSA was one of the world's most prevalent antibiotic-resistant bacteria. Among hospitalized patients and community members, MRSA is the cause of a significant number of infections. As a result of its resistance to classical beta-lactam and, in some cases, vancomycin antibiotics, efforts must be made as soon as feasible to find a new approach to fighting MRSA. Purpose: This study is designed to evaluate the antibacterial activity of quinoxaline derivative compound against MRSA in comparison with vancomycin as a reference drug. Methods: Sixty MRSA isolates were subjected to susceptibility testing by broth microdilution method for quinoxaline derivative compound and vancomycin. Each drug's minimal inhibitory concentration (MIC) was determined and compared. Results: Among the sixty MRSA isolates, most of the quinoxaline derivative compound MIC findings (56.7%) were 4 µg/mL compared to vancomycin MIC values (63.3%) of 4 µg/mL. In comparison, 20% of quinoxaline derivative compound MIC readings were 2 µg/mL, while the vancomycin MIC results were 6.7%. However, the overall proportion of MIC readings at ≤2 µg/mL for both antibacterial agents was equal (23.3%). None of the isolates were resistant to vancomycin. Conclusion: This experiment revealed that most MRSA isolates were associated with low MICs (1-4 µg/mL) for quinoxaline derivative compound. Overall, the susceptibility of the quinoxaline derivative compound signifies a promising efficacy against MRSA and may set a novel treatment approach.
