{"title":"新型唑类化合物（ATTAF-1和ATTAF-2）在小鼠模型中对抗系统性念珠菌感染的体内效率。","authors":"Hamed Fakhim , Afsane Vaezi , Hamid Morovati , Azadeh Bandegani , Kiana Abbasi , Saeed Emami , Davood Nasiry , Seyedeh Mahdieh Hashemi , Fatemeh Ahangarkani , Hamid Badali","doi":"10.1016/j.mycmed.2023.101437","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><span>Antifungal resistance<span> is the main health concern in the control of invasive fungal infections<span>. This research was designed to further assess the antifungal activity<span> of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against </span></span></span></span><span><em>Candida albicans</em></span><span> systemic candidiasis in the murine model.</span></p></div><div><h3>Materials & methods</h3><p>The murine model of systemic candidiasis was designed via the inoculation of 1 × 10<sup>6</sup><span> CFU of </span><em>Candida albicans</em><span><span><span><span><span>. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The </span>median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via </span>histopathology staining) fungal burden was also assessed. Furthermore, </span>immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in </span>serum protein levels.</span></p></div><div><h3>Results</h3><p>ATTAFs considerably improved the survival of the murine model (<em>P</em> < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (<em>P</em> > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":14824,"journal":{"name":"Journal de mycologie medicale","volume":"33 4","pages":"Article 101437"},"PeriodicalIF":2.2000,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model\",\"authors\":\"Hamed Fakhim , Afsane Vaezi , Hamid Morovati , Azadeh Bandegani , Kiana Abbasi , Saeed Emami , Davood Nasiry , Seyedeh Mahdieh Hashemi , Fatemeh Ahangarkani , Hamid Badali\",\"doi\":\"10.1016/j.mycmed.2023.101437\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span>Antifungal resistance<span> is the main health concern in the control of invasive fungal infections<span>. This research was designed to further assess the antifungal activity<span> of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against </span></span></span></span><span><em>Candida albicans</em></span><span> systemic candidiasis in the murine model.</span></p></div><div><h3>Materials & methods</h3><p>The murine model of systemic candidiasis was designed via the inoculation of 1 × 10<sup>6</sup><span> CFU of </span><em>Candida albicans</em><span><span><span><span><span>. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The </span>median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via </span>histopathology staining) fungal burden was also assessed. Furthermore, </span>immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in </span>serum protein levels.</span></p></div><div><h3>Results</h3><p>ATTAFs considerably improved the survival of the murine model (<em>P</em> < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (<em>P</em> > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":14824,\"journal\":{\"name\":\"Journal de mycologie medicale\",\"volume\":\"33 4\",\"pages\":\"Article 101437\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2023-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal de mycologie medicale\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1156523323000811\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MYCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal de mycologie medicale","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1156523323000811","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MYCOLOGY","Score":null,"Total":0}
In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model
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.
期刊介绍：
The Journal de Mycologie Medicale / Journal of Medical Mycology (JMM) publishes in English works dealing with human and animal mycology. The subjects treated are focused in particular on clinical, diagnostic, epidemiological, immunological, medical, pathological, preventive or therapeutic aspects of mycoses. Also covered are basic aspects linked primarily with morphology (electronic and photonic microscopy), physiology, biochemistry, cellular and molecular biology, immunochemistry, genetics, taxonomy or phylogeny of pathogenic or opportunistic fungi and actinomycetes in humans or animals. Studies of natural products showing inhibitory activity against pathogenic fungi cannot be considered without chemical characterization and identification of the compounds responsible for the inhibitory activity.
JMM publishes (guest) editorials, original articles, reviews (and minireviews), case reports, technical notes, letters to the editor and information. Only clinical cases with real originality (new species, new clinical present action, new geographical localization, etc.), and fully documented (identification methods, results, etc.), will be considered.
Under no circumstances does the journal guarantee publication before the editorial board makes its final decision.
The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey platforms.
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