Synthesis, Cytotoxicity Evaluation, and Antifungal Activity of Novel Nitroglycerin Derivatives against Clinical Isolates.

BACKGROUND

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 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 isolates and four standard 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 and genes under nitroglycerin derivatives-treated and untreated conditions.

RESULTS

The derivatives 1b and 2b exhibited potent antifungal activity against 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 and genes in all susceptible and resistant isolates.

CONCLUSION

Considering the potential and efficacy of these compounds against clinical isolates, the complementary and clinical trials should be investigated.