Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. General Procedure for the Synthesis of Benzylidenemalononitriles (3a–c)
3.1.1. 2-(3,4,5-trimethoxybenzylidene)malononitrile (3a)
3.1.2. 2-(4-nitrobenzylidene)malononitrile (3b)
3.1.3. 2-(4-bromobenzylidene)malononitrile (3c)
3.2. General Procedure for the Preparation of Hydrazone Derivatives (1a–o)
3.2.1. 1-(2-(trifluoromethyl)phenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1a)
3.2.2. 1-(2-methoxyphenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1b)
3.2.3. 1-(2-bromophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1c)
3.2.4. 1-(2-chlorophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1d)
3.2.5. 1-(2,4-dichlorophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1e)
3.2.6. 1-(2,4-difluorophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1f)
3.2.7. 1-(o-tolyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1g)
3.2.8. 1-(4-chlorophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1h)
3.2.9. 1-(2-fluorophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1i)
3.2.10. 1-(pentafluorophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1j)
3.2.11. 1-(4-bromophenyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1k)
3.2.12. 1-(p-tolyl)-2-(3,4,5-trimethoxybenzylidene)hydrazine (1l)
3.2.13. 1-(2-methoxyphenyl)-2-(4-nitrobenzylidene)hydrazine (1m)
3.2.14. 1-(4-bromobenzylidene)-2-phenylhydrazine (1n)
3.2.15. 1-(4-bromobenzylidene)-2-(3,4-dimethylphenyl)hydrazine (1o)
3.3. X-ray Crystallography
3.4. MIC99 Determination Assays
3.5. Cell Viability Assay
3.6. Cancer Cell Proliferation Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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MIC Values (µg/mL) on Candida spp. [a,b,c,d] | |||||||||
---|---|---|---|---|---|---|---|---|---|
Entry | Compound | C. albicans SC5314 | C. dubliniensis | C. glabrata | C. parapsilosis | C. tropicalis | C. albicans (Mucoviscidosis) | C. albicans (R echinocandins) | C. glabrata (R azoles) |
1 | 1c | 32 | >32 [e] | 32 | 32 | >32 | >32 | >32 | 32 |
2 | 1d | 32 | >32 | 16 | >32 | >32 | >32 | >32 | 32 |
3 | 1i | 32 | >32 | 32 | 32 | >32 | >32 | >32 | 32 |
4 | 1k | 32 | >32 | 16 | 32 | 32 | >32 | >32 | >32 |
5 | 1l | 32 | >32 | 16 | 32 | 32 | >32 | >32 | 32 |
6 | Fluconazole | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | >32 |
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Negru, G.; Kamus, L.; Bîcu, E.; Shova, S.; Sendid, B.; Dubar, F.; Ghinet, A. Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains. Molecules 2021, 26, 5861. https://doi.org/10.3390/molecules26195861
Negru G, Kamus L, Bîcu E, Shova S, Sendid B, Dubar F, Ghinet A. Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains. Molecules. 2021; 26(19):5861. https://doi.org/10.3390/molecules26195861
Chicago/Turabian StyleNegru, Georgiana, Laure Kamus, Elena Bîcu, Sergiu Shova, Boualem Sendid, Faustine Dubar, and Alina Ghinet. 2021. "Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains" Molecules 26, no. 19: 5861. https://doi.org/10.3390/molecules26195861