A novel series of thiazolyl–pyrazoline derivatives: Synthesis and evaluation of antifungal activity, cytotoxicity and genotoxicity

• Published in: European journal of medicinal chemistry 2015-03, Vol.92, p.342-352
• Main Authors: Altıntop, Mehlika Dilek, Özdemir, Ahmet, Turan-Zitouni, Gülhan, Ilgın, Sinem, Atlı, Özlem, Demirel, Rasime, Kaplancıklı, Zafer Asım
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Antifungal activity; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Aspergillus niger - drug effects; Candida - drug effects; Cell Line; Cell Proliferation - drug effects; Cytotoxicity; Dose-Response Relationship, Drug; Fusarium - drug effects; Genotoxicity; Humans; Mice; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazoline; Structure-Activity Relationship; Thiazole; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.12.055

In the current work, new thiazolyl–pyrazoline derivatives (1–22) were synthesized and evaluated for their antifungal effects against pathogenic yeasts and molds using a broth microdilution assay. Ames assay was carried out to determine the genotoxicity of the most effective antifungal derivatives. The cytotoxicity of the compounds (1–22) was also investigated against A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cells. Among these derivatives, 2-[5-(4-fluorophenyl)-3-(5-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4-methylsulfonylphenyl)thiazole (18) can be identified as the most promising anticandidal derivative due to its notable inhibitory effect on Candida zeylanoides with a MIC value of 250 μg/mL when compared with ketoconazole (MIC = 250 μg/mL), low cytotoxicity against NIH/3T3 cells and non-mutagenic effect. On the other hand, 2-[5-(4-fluorophenyl)-3-(5-chlorothiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-(4-bromophenyl)thiazole (4) can be considered as the most promising anticancer agent against A549 cancer cells owing to its notable inhibitory effect on A549 cells with an IC50 value of 62.5 μg/mL when compared with cisplatin (IC50 = 45.88 μg/mL) and low cytotoxicity against NIH/3T3 cells. New thiazolyl–pyrazoline derivatives were synthesized and evaluated for their antifungal activity and cytotoxicity against A549 and NIH/3T3 cells. The genotoxicity of the most effective antifungal compounds was also investigated. [Display omitted] •The compounds were tested in vitro against pathogenic yeasts and molds.•Genotoxicity of the most effective antifungal agents was evaluated.•Each derivative was evaluated for its cytotoxicity against A549 and NIH/3T3 cells.•Compound 18 was the most promising anticandidal derivative.•Compound 4 was the most effective anticancer agent against A549 cell lines.