The Combination of 3-Hydrazinoquinoxaline-2-Thiol with Thymoquinone Demonstrates Synergistic Activity Against Different Candida Strains.

ABSTRACT

Introduction: Candida is the primary cause of invasive fungal disease, candidiasis, especially in developed nations. The increasing resistance observed in multiple antibiotics, coupled with the prolonged process of creating new antibiotics from the ground up, emphasizes the urgent requirement for innovative methods and new compounds to combat Candida infections. Employing a treatment strategy that combines antibiotics can improve efficacy, broaden the spectrum of targeted fungal, and reduce the chances of resistance emergence. This approach shows potential in tackling the escalating problem of antibiotic resistance. The objective of this research is to explore the potential synergistic effects of combining 3-hydrazinoquinoxaline-2-thiol and thymoquinone against a variety of Candida isolates. This investigation aims to offer an understanding of the collective antimicrobial action of these compounds. Methods: Broth microdilution was utilized to assess the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and thymoquinone for 22 clinical Candida isolates. Following this, a checkerboard assay was employed to analyze the interaction between 3-hydrazinoquinoxaline-2-thiol and thymoquinone, with a specific focus on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of thymoquinone and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical Candida strains, with thymoquinone exhibiting MICs ranging from 64 to 8 µg/mL, and 3-hydrazinoquinoxaline-2-thiol displaying MICs varying from 64 to 8 µg/mL. Notably, the combination of 3-hydrazinoquinoxaline-2-thiol and thymoquinone resulted in a synergistic effect, leading to a significant reduction in MICs, with reductions of up to 64-fold with FICI below 0.5 against tested strains. Conclusion: The prospect of using 3-hydrazinoquinoxaline-2-thiol in combination with thymoquinone as an effective solution against Candida looks encouraging. Nevertheless, to validate its practical applicability, additional comprehensive testing and experiments are imperative.