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In-Vivo Efficiency of the Novel Azole Compounds (Attaf-1 and Attaf-2) Against Systemic Candidiasis in a Murine Model Publisher Pubmed



Fakhim H1 ; Vaezi A2 ; Morovati H3 ; Bandegani A4 ; Abbasi K5 ; Emami S6 ; Nasiry D7 ; Hashemi SM6 ; Ahangarkani F8 ; Badali H9
Authors
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Authors Affiliations
  1. 1. Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  5. 5. Department of Microbiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran
  6. 6. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
  7. 7. Amol Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Iran
  8. 8. Antimicrobial Resistance Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
  9. 9. Department of Molecular Microbiology & Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, United States

Source: Journal of Medical Mycology Published:2023


Abstract

Background: Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model. Materials & methods: The murine model of systemic candidiasis was designed via the inoculation of 1 × 106 CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels. Results: ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver. Conclusion: Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes. © 2023 SFMM
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