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The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues
Author(s) -
Zoidis Grigoris,
Kritsi Eftichia,
Lecinska Paulina,
Ivanov Marija,
Zoumpoulakis Panagiotis,
Sokovic Marina,
Catto Marco
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000312
Subject(s) - ketoconazole , itraconazole , aspergillus fumigatus , triazole , candida krusei , candida albicans , chemistry , stereochemistry , quantitative structure–activity relationship , antifungal drug , antifungal , pharmacology , biology , microbiology and biotechnology , corpus albicans , organic chemistry
The significant antifungal activity of a series of novel 1,2,4‐triazole derivatives against different strains of Candida albicans , Candida krusei and Aspergillus fumigatus , compared to the commercial fungicides ketoconazole and itraconazole, is reported. Systemic mycosis and invasive fungal infections, whether from immunodeficiency or hospital‐acquired infection, have been on an upward trend for several years. The 1,2,4‐triazole ring substituted with other aromatic and heteroaromatic systems plays an important role in the field of antifungal drug discovery and development. Thus, an extensive series of 29 triazoles, substituted in different positions with a variety of aromatic rings, has been designed, synthesized, and evaluated for their fungicidal activity. Almost all the agents tested in vitro showed high activity against all examined fungal strains. It is noteworthy that, in the case of A. fumigatus , all the examined compounds achieved equal or higher antifungal activity than ketoconazole, but less activity than itraconazole. Among all the derivatives studied, the dichlorourea analogue and bromo‐substituted triazole stand out as the most promising compounds. Quantitative structure‐activity relationship (QSAR) models were built for a systematic structure‐activity relationship (SAR) profile to explain and potentially explore the potency characteristics of 1,2,4‐triazole analogues.