In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model

• Published in: Journal de mycologie médicale 2023-11, Vol.33 (4), p.101437-101437, Article 101437
• Main Authors: Fakhim, Hamed, Vaezi, Afsane, Morovati, Hamid, Bandegani, Azadeh, Abbasi, Kiana, Emami, Saeed, Nasiry, Davood, Hashemi, Seyedeh Mahdieh, Ahangarkani, Fatemeh, Badali, Hamid
• Format: Article
• Language: English
• Subjects: Animals; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungal Agents - therapeutic use; Azoles - pharmacology; Azoles - therapeutic use; Candida albicans; Candidiasis, Invasive - drug therapy; Disease Models, Animal; Drug Resistance, Fungal; Fluconazole - pharmacology; Fluconazole - therapeutic use; Humans; Mice; Microbial Sensitivity Tests; Murine model; Systemic candidiasis; Triazole derivatives
• ISSN: 1156-5233; 1773-0449
• DOI: 10.1016/j.mycmed.2023.101437

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. 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. 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. 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.