1,3,4-Thiadiazole and 1,2,4-triazole-3(4 H )-thione bearing salicylate moiety: synthesis and evaluation as anti- Candida albicans

Awwad Abdoh Radwan,Fares Kaed Alanazi,Mohammed Hamed Al-Agamy

doi:10.1590/s2175-97902017000115239

Awwad Abdoh Radwan, Fares Kaed Alanazi + Show 1 more

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https://doi.org/10.1590/s2175-97902017000115239

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Abstract

Dramatically increased occurrence of both superficial and invasive fungal infections has been observed. Candida albicans appear to be the main etiological agent of invasive fungal infections. The anti-C. albicans activity of thiosemicarbazide, 1,3,4-Thiadiazole, and 1,2,4-triazole-3(4H)-thione compounds (compounds 3-23) were investigated. The MIC values of thiadiazole and triazole derivatives 10-23 were in the range of 0.08-0.17 µmol mL-1, while that of fluconazole was 0.052 µmol mL-1. Compound 11 (5-(2-(4-chlorobenzyloxy)phenyl)-N-allyl-1,3,4-thiadiazol-2-amine) and compound 18 (5-(2-(4-chlorobenzyloxy)phenyl)-4-allyl-2H-1,2,4-triazole-3(4H)-thione) were found to be the most active compounds, with MIC values of 0.08 µmol mL-1. The newly synthesized thiadiazole and triazole compounds (compounds 10-23) showed promising anti-Candida activity. The allyl substituent-bearing compounds 11 and 18 exhibited significant anti-Candida albicans activity and showed a binding mode as well as the fluconazole x-ray structure.

Highlights

Over the last two decades, dramatically increased occurrence of both superficial and invasive fungal infections has been observed
The chemical structures of the synthesized compounds were in accordance with their 1H and 13C NMR spectra
The spectral data are summarized in the material and methods section. 1H NMR and 13C NMR spectra were measured in dimethylsulfoxide-d6 for compounds 2-23 at ambient temperature. 1H NMR spectrum of compound 2 showed

Summary

Introduction

Over the last two decades, dramatically increased occurrence of both superficial and invasive fungal infections has been observed. In organ transplant cases and in immune compromised individuals, including patients with cancer or AIDS, fungal infections are the major cause of morbidity and mortality (Romani, 2008). The invasive Candida infections are mainly caused by Candida albicans and account for 30-40% of fungal infectionrelated mortality (Pfaller, Diekema, 2010). A major obstacle in the treatment of Candida infections is the spread of anti-Candida drug resistance following long-term regular administration of antimycotic therapy in severely immunocompromised subjects, such as cancer patients, transplant recipients, and patients undergoing surgery. In spite of the development of new drugs, such as new azole or echinocandin derivatives, Braz.

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