Infection and Drug Resistance (Jun 2024)
The Combination of 3-Hydrazinoquinoxaline-2-Thiol with Thymoquinone Demonstrates Synergistic Activity Against Different Candida Strains
Abstract
Mohammed A Bazuhair,1,2 Mohammed Alsieni,1 Hani Abdullah,3 Jawahir A Mokhtar,3– 5 Dalya Attallah,4 Turki S Abujamel,5,6 Khalil K Alkuwaity,5,6 Hanouf A Niyazi,3 Hatoon A Niyazi,3 Hind AbdulMajed,3 Noha Juma,3 Mohammed W Al-Rabia,3 Abdelbagi Alfadil,2,3 Karem Ibrahem3 1Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 2Centre of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Clinical Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, 21589, Saudi Arabia; 5Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Karem Ibrahem, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia, Tel +966 562525685, Email [email protected]: 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.Keywords: Candida spp, antimicrobial resistance, 3-hydrazinoquinoxaline-2-thiol, thymoquinone, MIC, FICI
