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Synthesis, Cytotoxicity Evaluation, and Antifungal Activity of Novel Nitroglycerin Derivatives Against Clinical Candida Albi-Cans Isolates



Rashidi N1 ; Rezaie S1 ; Hashemi SJ1 ; Habibi A2 ; Baghersad MH3 ; Daie R1 ; Khodavaisy S1 ; Bakhshi H1 ; Salimi A4 ; Getso ME1 ; Rafat Z1
Authors
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Authors Affiliations
  1. 1. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Chemistry, Faculty of Chemistry, Kharazmi University, Tehran, Iran
  3. 3. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
  4. 4. Nanobiotechnology Reserch Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

Source: Iranian Journal of Public Health Published:2021

Abstract

Background: Candida albicans remains the main cause of candidiasis in most clinical settings. Available drugs for candidiasis treatment have many side effects. In this work, novel nitroglycerin derivatives were synthesized and their cytotoxic and antifungal effects evaluated against fluconazole susceptible and resistant clinical C. albi-cans isolates. Methods: This experimental study was performed in Tehran University of Medical Sciences and Baqiatallah University of Medical Sciences, Tehran, Iran between Feb to Dec 2019. The in vitro activities of two novel nitroglycerin derivatives (1b and 2b) against 25 clinical fluconazole-susceptible and resistant C. albicans isolates and four standard C. albicans strains were determined according to CLSI reference M27-A3 documents. The cytotoxicity of chemical compounds was investigated near the SNL76/7 cells by colorimetric assay. Real-time PCRs were performed to evaluate the alterations in the regulation of ERG11 and CDR1 genes under nitroglycerin derivatives-treated and untreated conditions. Results: The derivatives 1b and 2b exhibited potent antifungal activity against C. albicans isolates; MICs and MFCs varied from 18 μg/ml to 72 μg/ml and 36 μg/ml to 144 μg/ml, respectively. The cell viability evaluation demonstrated that both chemical compounds are safe within 24h. The nitroglycerin derivatives were able to reduce the transcription level of CDR1 and ERG11 genes in all susceptible and resistant C. albicans isolates. Conclusion: Considering the potential and efficacy of these compounds against clinical C. albicans isolates, the complementary in vivo and clinical trials should be investigated. © 2021 Rashidi et al.
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