Περίληψη:
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. © 2020 Wiley-VCH GmbH
Συγγραφείς:
Zoidis, G.
Kritsi, E.
Lecinska, P.
Ivanov, M.
Zoumpoulakis, P.
Sokovic, M.
Catto, M.
Λέξεις-κλειδιά:
1 (4 chlorophenyl) 3 [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]urea; 1 phenyl 3 [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]urea; 2 (naphthalen 2 yl) n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]acetamide; 2 phenyl n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]acetamide; 2,4 dichloro n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]benzamide; 3 (2 chloro 6 fluorobenzyl) 5 (4 chlorophenyl) 1h 1,2,4 triazole; 3 (3,4 dichlorobenzyl) 5 phenyl 1h 1,2,4 triazole; 3 (4 bromobenzyl) 5 phenyl 1h 1,2,4 triazole; 3 (4 methoxybenzyl) 5 phenyl 1h 1,2,4 triazole; 3 (benzo[d][1,3]dioxol 5 ylmethyl) 5 (4 chlorophenyl) 1h 1,2,4 triazole; 3 (biphenyl 4 ylmethyl) 5 (4 chlorophenyl) 1h 1,2,4 triazole; 3 benzyl 5 (thiophen 2 yl) 1h 1,2,4 triazole; 3 benzyl 5 phenyl 1h 1,2,4 triazole; 3 chloro n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]benzamide; 3 phenyl n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]propanamide; 3 [[5 (3 chlorophenyl) 1h 1,2,4 triazol 3 yl]methyl]aniline; 3 [[5 (4 chlorophenyl) 1h 1,2,4 triazol 3 yl]methyl]aniline; 3,5 dibenzyl 1h 1,2,4 triazole; 4 (3 benzyl 1h 1,2,4 triazol 5 yl)pyridine; 4 methyl n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]benzenesulfonamide; 4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]aniline; 4 [[5 (4 chlorophenyl) 1h 1,2,4 triazol 3 yl]methyl]aniline; 5 (4 chlorophenyl) 3 (4 methoxybenzyl) 1h 1,2,4 triazole; antifungal agent; itraconazole; ketoconazole; n (3 chlorophenyl) n1 [3 [5 (3 chlorophenyl) 1h 1,2,4 triazol 3 yl]methyl]phenylurea; n (3 chlorophenyl) n1 [3 [5 (4 chlorophenyl) 4h 1,2,4 triazol 3 yl]methyl]phenylurea; n [3 [[5 (3 chlorophenyl) 1h 1,2,4 triazol 3 yl]methyl]phenyl]benzamide; n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]benzamide; n [4 [(5 phenyl 1h 1,2,4 triazol 3 yl)methyl]phenyl]cyclohexane carboxamide; triazole derivative; unclassified drug; antifungal agent; itraconazole; triazole derivative, Article; Aspergillus fumigatus; Candida albicans; controlled study; cycloaddition; dipole; drug synthesis; fungicidal activity; hydrogen bond; microwave cooking; minimum fungicidal concentration; minimum inhibitory concentration; nonhuman; Pichia kudriavzevii; priority journal; quantitative structure activity relation; reaction time; chemistry; drug effect; microbial sensitivity test; quantitative structure activity relation; synthesis, Antifungal Agents; Aspergillus fumigatus; Candida albicans; Itraconazole; Microbial Sensitivity Tests; Quantitative Structure-Activity Relationship; Triazoles
