Design, Synthesis, and Biological Evaluation of N′-Phenylhydrazides as Potential Antifungal Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Design and Synthesis of N′-Phenylhydrazides
2.2. Evaluation of Antifungal Activity In Vitro
2.2.1. Antifungal Activity of Target Compounds
2.2.2. The Inhibitory Efficiency of Compounds with Better Antifungal Activity
2.2.3. The Analysis of Preliminary SARs
2.3. The Investigation of the Antifungal Mechanism
2.3.1. Assay of Free Radical Scavenging
2.3.2. Production of ROS
2.3.3. Effects of A11 on Hyphal Morphology
2.3.4. Preliminary Antifungal Mechanisms
3. Materials and Methods
3.1. Materials
3.2. The Synthetic Procedure
3.2.1. Synthesis of Substituted Phenylhydrazine Hydrochloride
3.2.2. Synthesis of N′-Phenylhydrazides
3.3. Antifungal Activity In Vitro
3.3.1. Determination of MIC80 and MFC Value
3.3.2. Time–Inhibition Rate Curves
3.4. The Investigation of the Antifungal Mechanism
3.4.1. Scavenging of Free Radicals Generated from A11
3.4.2. Production of ROS
3.4.3. Analysis of the Mycelial Morphology
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Dartois, V.A.; Rubin, E.J. Anti-tuberculosis Treatment Strategies and Drug Development: Challenges and Priorities. Nat. Rev. Microbiol. 2022, 20, 685–701. [Google Scholar] [CrossRef]
- Zhang, Y.; Li, Q.H.; Chao, W.; Qin, Y.L.; Chen, J.Y.; Wang, Y.W.; Liu, R.H.; Lv, Q.Z.; Wang, J.X. Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo. Molecules 2022, 27, 4450. [Google Scholar] [CrossRef] [PubMed]
- Costa, D.S.; Rodrigues, A.G. Candida albicans Antifungal Resistance and Tolerance in Bloodstream Infections: The Triad Yeast-Host-Antifungal. Microorganisms 2020, 8, 154. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Puumala, E.; Robbins, N.; Cowen, L.E. Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond. Chem. Rev. 2021, 121, 3390–3411. [Google Scholar] [CrossRef]
- Wijnants, S.; Vreys, J.; Van Dijck, P. Interesting Antifungal Drug Targets in the Central Metabolism of Candida albicans. Trends Pharmacol. Sci. 2022, 43, 69–79. [Google Scholar] [CrossRef] [PubMed]
- Nobile, C.J.; Johnson, A.D. Candida albicans Biofilms and Human Disease. Annu. Rev. Microbiol. 2015, 69, 71–92. [Google Scholar] [CrossRef] [PubMed]
- Xiao, M.; Sun, Z.Y.; Kang, M.; Guo, D.W.; Liao, K.; Chen, S.C.; Kong, F.; Fan, X.; Cheng, J.W.; Hou, X.; et al. Five-Year National Surveillance of Invasive Candidiasis: Species Distribution and Azole Susceptibility from the China Hospital Invasive Fungal Surveillance Net (ChIF-NET) Study. J. Clin. Microbiol. 2018, 56, e00577-18. [Google Scholar] [CrossRef] [PubMed]
- Mukaremera, L.; Lee, K.K.; Mora, M.H.M.; Gow, N.A.R. Candida albicans Yeast, Pseudohyphal, and Hyphal Morphogenesis Differentially Affects Immune Recognition. Front. Immunol. 2017, 8, 629. [Google Scholar] [CrossRef] [PubMed]
- Tits, J.; Cammue, B.P.A.; Thevissen, K. Combination Therapy to Treat Fungal Biofilm-Based Infections. Int. J. Mol. Sci. 2020, 21, 8873. [Google Scholar] [CrossRef] [PubMed]
- Mahboub, H.H.; Eltanahy, A.; Omran, A.; Mansour, A.T.; Safhi, F.A.; Alwutayd, K.M.; Khamis, T.; Husseiny, W.A.; Ismail, S.H.; Yousefi, M.; et al. Chitosan Nanogel Aqueous Treatment Improved Blood Biochemicals, Antioxidant Capacity, Immune Response, Immune-Related Gene Expression and Infection Resistance of Nile Tilapia. Comp. Biochem. Physiol. Biochem. Mol. Biol. 2024, 269, 110876. [Google Scholar] [CrossRef]
- Li, J.; Buchner, J. Structure, Function and Regulation of the Hsp90 Machinery. Biomed. J. 2013, 36, 106–117. [Google Scholar]
- Lee, K.H.; Park, S.J.; Choi, S.J.; Park, J.Y. Proteus Vulgaris and Proteus Mirabilis Decrease Candida albicans Biofilm Formation by Suppressing Morphological Transition to Its Hyphal Form. Yonsei Med. J. 2017, 58, 1135–1143. [Google Scholar] [CrossRef]
- Arendrup, M.C.; Patterson, T.F. Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment. J. Infect. Dis. 2017, 216, S445–S451. [Google Scholar] [CrossRef]
- White, P.L.; Dhillon, R.; Hughes, H.; Wise, M.P.; Backx, M. COVID-19 and Fungal Infection: The Need for a Strategic Approach. Lancet Microbe 2020, 1, e196. [Google Scholar] [CrossRef]
- Murphy, S.E.; Bicanic, T. Drug Resistance and Novel Therapeutic Approaches in Invasive Candidiasis. Front. Cell. Infect. Microbiol. 2021, 11, 759408. [Google Scholar] [CrossRef]
- Maubon, D.; Garnaud, C.; Calandra, T.; Sanglard, D.; Cornet, M. Resistance of Candida spp. to Antifungal Drugs in the Icu: Where Are We Now? Intensive Care Med. 2014, 40, 1241–1255. [Google Scholar] [CrossRef]
- Hoang, A. Caspofungin Acetate: An Antifungal Agent. Am. J. Health-Syst. Pharm. 2001, 58, 1206–1214. [Google Scholar] [CrossRef]
- Richardson, K.; Cooper, K.; Marriott, M.S.; Tarbit, M.H.; Troke, P.F.; Whittle, P.J. Discovery of Fluconazole, a Novel Antifungal Agent. Rev. Infect. Dis. 1990, 12 (Suppl. S3), S267–S271. [Google Scholar] [CrossRef]
- Boken, D.J.; Swindells, S.; Rinaldi, M.G. Fluconazole-Resistant Candida albicans. Clin. Infect. Dis. 1993, 17, 1018–1021. [Google Scholar] [CrossRef]
- Pasquale, T.; Tomada, J.R.; Ghannoun, M.; Dipersio, J.; Bonilla, H. Emergence of Candida tropicalis Resistant to Caspofungin. J. Antimicrob. Chemother. 2008, 61, 219. [Google Scholar] [CrossRef]
- Sawant, B.; Khan, T. Recent Advances in Delivery of Antifungal Agents for Therapeutic Management of Candidiasis. Biomed. Pharmacother. 2017, 96, 1478–1490. [Google Scholar] [CrossRef] [PubMed]
- Carmo, A.; Rocha, M.; Pereirinha, P.; Tomé, R.; Costa, E. Antifungals: From Pharmacokinetics to Clinical Practice. Antibiotics 2023, 12, 884. [Google Scholar] [CrossRef]
- Tirapegui, C.; Acevedo, F.W.; Dahech, P.; Torrent, C.; Barrias, P.; Rojas, P.M.; Mascayano, C. Easy and Rapid Preparation of Benzoylhydrazides and Their Diazene Derivatives as Inhibitors of 15-Lipoxygenase. Bioorg. Med. Chem. Lett. 2017, 27, 1649–1653. [Google Scholar] [CrossRef]
- Clements, J.S.; Islam, R.; Sun, B.; Tong, F.; Gross, A.D.; Bloomquist, J.R.; Carlier, P.R. N′-Mono- and N, N′-Diacyl Derivatives of Benzyl and Arylhydrazines as Contact Insecticides against Adult Anopheles Gambiae. Pestic. Biochem. Physiol. 2017, 143, 33–38. [Google Scholar] [CrossRef]
- Kozlov, M.V.; Konduktorov, K.A.; Shcherbakova, A.S.; Kochetkov, S.N. Synthesis of N′-Propylhydrazide Analogs of Hydroxamic Inhibitors of Histone Deacetylases (HDACs) and Evaluation of Their Impact on Activities of Hdacs and Replication of Hepatitis C Virus (HCV). Bioorg. Med. Chem. Lett. 2019, 29, 2369–2374. [Google Scholar] [CrossRef]
- Nam, G.; Suh, J.M.; Yi, Y.; Lim, M.H. Drug Repurposing: Small Molecules against Cu(II)–Amyloid-β and Free Radicals. J. Inorg. Biochem. 2021, 224, 111592. [Google Scholar] [CrossRef]
- Wu, Y.Y.; Shao, W.B.; Zhu, J.J.; Long, Z.Q.; Liu, L.W.; Wang, P.Y.; Li, Z.; Yang, S. Novel 1,3,4-Oxadiazole-2-Carbohydrazides as Prospective Agricultural Antifungal Agents Potentially Targeting Succinate Dehydrogenase. J. Agric. Food Chem. 2019, 67, 13892–13903. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.Z.; Drewe, J.; Tseng, B.; Kasibhatla, S.; Cai, S.X. Discovery and Sar of Indole-2-Carboxylic Acid Benzylidene-Hydrazides as a New Series of Potent Apoptosis Inducers Using a Cell-Based Hts Assay. Bioorg. Med. Chem. 2004, 12, 3649–3655. [Google Scholar] [CrossRef]
- Turan, Z.G.; Altintop, M.D.; Ozdemir, A.; Demirci, F.; Abu, M.U.; Kaplancikli, Z.A. Synthesis and Antifungal Activity of New Hydrazide Derivatives. J. Enzym. Inhib. Med. Chem. 2013, 28, 1211–1216. [Google Scholar] [CrossRef] [PubMed]
- Pham, V.H.; Phan, T.P.D.; Phan, D.C.; Vu, B.D. Synthesis and Bioactivity of Hydrazide-Hydrazones with the 1-Adamantyl-Carbonyl Moiety. Molecules 2019, 24, 4000. [Google Scholar] [CrossRef]
- Ganrot, P.O.; Rosengren, E.; Gottfries, C.G. Effect of Iproniazid on Monoamines and Monamine Oxidase in Human Brain. Experientia 1962, 18, 260–261. [Google Scholar] [CrossRef] [PubMed]
- Jacob, N.; Guillemard, L.; Wencel, D.J. Highly Efficient Synthesis of Hindered 3-Azoindoles via Metal-Free C-H Functionalization of Indoles. Synthesis 2020, 52, 574–580. [Google Scholar] [CrossRef]
- Espinel-Ingroff, A.; Canton, E.; Peman, J.; Rinaldi, M.G.; Fothergill, A.W. Comparison of 24-Hour and 48-Hour Voriconazole Mics as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) in Three Laboratories: Results Obtained with 2162 Clinical Isolates of Candida spp. and Other Yeasts. J. Clin. Microbiol. 2009, 47, 2766–2771. [Google Scholar]
- Iqbal, N.J.; Boey, A.; Park, B.J.; Brandt, M.E. Determination of in Vitro Susceptibility of Ocular Fusarium spp. Isolates from Keratitis Cases and Comparison of Clinical and Laboratory Standards Institute M38-A2 and E Test Methods. Diagn. Microbiol. Infect. Dis. 2008, 62, 348–350. [Google Scholar] [CrossRef] [PubMed]
- Yang, S.S.; Lv, Q.Y.; Fu, J.; Zhang, T.Y.; Du, Y.S.; Yang, X.J.; Zhou, L. New 7-Chloro-9-Methyl-2-Phenyl-3,4-Dihydro-Β-Carbolin-2-Iums as Promising Fungicide Candidates: Design, Synthesis, and Bioactivity. J. Agric. Food Chem. 2022, 70, 4256–4266. [Google Scholar] [CrossRef] [PubMed]
- Luque, C.J.C.; Rodríguez, Z.P.; López, O.J.C.; Garzón, I.L. Revisiting the Scavenging Activity of Glutathione: Free Radicals Diversity and Reaction Mechanisms. Comput. Theor. Chem. 2023, 1227, 114227. [Google Scholar] [CrossRef]
- Wang, D.; Zhang, J.; Jia, X.M.; Xin, L.; Zhai, H. Antifungal Effects and Potential Mechanism of Essential Oils on Collelotrichum gloeosporioides In Vitro and In Vivo. Molecules 2019, 24, 3386. [Google Scholar] [CrossRef] [PubMed]
- Kalgutkar, A.S.; Gardner, I.; Obach, R.S.; Shaffer, C.L.; Callegari, E.; Henne, K.R.; Mutlib, A.E.; Dalvie, D.K.; Lee, J.S.; Nakai, Y.; et al. A Comprehensive Listing of Bioactivation Pathways of Organic Functional Groups. Curr. Drug Metab. 2005, 6, 161–225. [Google Scholar] [CrossRef] [PubMed]
- Kakizaki, T.; Abe, H.; Kotouge, Y.; Matsubuchi, M.; Sugou, M.; Honma, C.; Tsukuta, K.; Satoh, S.; Shioya, T.; Nakamura, H.; et al. Live-Cell Imaging of Septins and Cell Polarity Proteins in the Growing Dikaryotic Vegetative Hypha of the Model Mushroom Coprinopsis Cinerea. Sci. Rep. 2023, 13, 10132. [Google Scholar] [CrossRef]
- Triastuti, A.; Vansteelandt, M.; Barakat, F.; Amasifuen, C.; Jargeat, P.; Haddad, M. Untargeted Metabolomics to Evaluate Antifungal Mechanism: A Study of Cophinforma mamane and Candida albicans Interaction. Nat. Prod. Bioprospect. 2023, 13, 1. [Google Scholar] [CrossRef]
- Zhang, Y.H.; Yang, S.S.; Zhang, Q.; Zhang, T.T.; Zhang, T.Y.; Zhou, B.H.; Zhou, L. Discovery of N-Phenylpropiolamide as a Novel Succinate Dehydrogenase Inhibitor Scaffold with Broad-Spectrum Antifungal Activity on Phytopathogenic Fungi. J. Agric. Food Chem. 2023, 71, 3681–3693. [Google Scholar] [CrossRef] [PubMed]
- Afri, M.; Frimer, A.A.; Cohen, Y. Active Oxygen Chemistry within the Liposomal Bilayer Part Iv: Locating 2′,7′-Dichlorofluorescein (DCF), 2′,7′-Dichlorodihydrofluorescein (DCFH) and 2′,7′-Dichlorodihydrofluorescein Diacetate (DCFH-DA) in the Lipid Bilayer. Chem. Phys. Lipids 2004, 131, 123–133. [Google Scholar] [CrossRef]
- Zhang, J.Q.; Huang, G.B.; Weng, J.; Lu, G.; Chan, A.S.C. Copper(II)-Catalyzed Coupling Reaction: An Efficient and Regioselective Approach to N′,N′-Diaryl Acylhydrazines. Org. Biomol. Chem. 2015, 13, 2055–2063. [Google Scholar] [CrossRef]
- Huang, Z.Y.; Zhang, Q.Q.; Zhao, Q.G.; Yu, W.Q.; Chang, J.B. Synthesis of 2-Imino-1,3,4-Thiadiazoles from Hydrazides and Isothiocyanates via Sequential Oxidation and P(NMe2)3-Mediated Annulation Reactions. Org. Lett. 2020, 22, 4378–4382. [Google Scholar] [CrossRef]
- Shuler, W.G.; Smith, E.A.; Hess, S.M.; McFadden, T.M.C.; Metz, C.R.; Van Derveer, D.G.; Pennington, W.T.; Mabe, P.J.; Knick, S.L.; Beam, C.F. Preparation and X-Ray Crystal Structure of 3-(4-(Dimethylamino)Phenyl)-2-(Phenylamino)Isoquinolin-1(2h)-One, 3-(4-Methoxyphenyl)-2-(Phenylamino)Isoquinolin-1(2h)-One, and 2-Methyl-N′-(4-Methylbenzoyl)-N′-Phenylbenzohydrazide from Polylithiated 2-Methylbenzoic Acid Phenylhydrazide and Methyl 4-Dimethylaminobenzoate, Methyl 4-Methoxybenzoate, or Methyl 4-Methylbenzoate. J. Chem. Crystallogr. 2012, 42, 952–959. [Google Scholar]
- Wang, T.T.; Gao, F.; Xue, M.; Song, Y.J.; Wang, W.H. Ethyl 3-(2-Chlorophenyl)-5-(Diethoxyphosphinoyl)-1-Phenyl-4,5-Dihydro-1h-Pyrazole-5-Carboxylate. Acta Crystallogr. Sect. E Struct. Rep. 2007, 63, o2549. [Google Scholar] [CrossRef]
- Liu, R.Y.; Li, Z.Z.; Liu, S.F.; Zheng, J.S.; Zhu, P.P.; Cheng, B.; Yu, R.J.; Geng, H.L. Synthesis, Structure–Activity Relationship, and Mechanism of a Series of Diarylhydrazide Compounds as Potential Antifungal Agents. J. Agric. Food Chem. 2023, 71, 6803–6817. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Jia, H.; Wang, B.; Xiao, Y.; Guo, H. Synthesis of Spirobidihydropyrazole through Double 1,3-Dipolar Cycloaddition of Nitrilimines with Allenoates. Org. Lett. 2017, 19, 4714–4717. [Google Scholar] [CrossRef] [PubMed]
- Huang, Z.Y.; Zhang, Q.Q.; Yi, X.F.; Zhao, Z.X.; Yu, W.Q.; Chang, J.B. Synthesis of 2-Imino-1,3,4-Selenadiazoles via Tributylphosphine-Mediated Annulation of N-Aroyldiazenes with Isoselenocyanates. Adv. Synth. Catal. 2021, 363, 4894–4898. [Google Scholar] [CrossRef]
- Wang, W.J.; Zhang, T.; Duan, L.J.; Zhang, X.J.; Yan, M. KOt-Bu Promoted Homocoupling and Decomposition of N′-Aryl Acylhydrazines: Synthesis of Unsymmetric N′,N′-Diaryl Acylhydrazines. Tetrahedron 2015, 71, 9073–9080. [Google Scholar] [CrossRef]
- Sun, Y.; Ling, S.H.; Duan, Y.B.; Li, J.X.; Chen, Z.K.; Wu, X.F. Synthesis of 5-Trifluoromethyl-1,4-Dihydro-1,2,4-Triazines via Base-Mediated [3+3] Cycloaddition of Nitrile Imines and Cf3-Imidoyl Sulfoxonium Ylides. Adv. Synth. Catal. 2023, 365, 1521–1525. [Google Scholar] [CrossRef]
- Voronin, V.V.; Ledovskaya, M.S.; Gordeev, E.G.; Rodygin, K.S.; Ananikov, V.P. [3 + 2]-Cycloaddition of in Situ Generated Nitrile Imines and Acetylene for Assembling of 1,3-Disubstituted Pyrazoles with Quantitative Deuterium Labeling. J. Org. Chem. 2018, 83, 3819–3828. [Google Scholar] [CrossRef] [PubMed]
- Areephong, J.; Mattson, K.M.; Treat, N.J.; Poelma, S.O.; Kramer, J.W.; Sprafke, H.A.; Latimer, A.A.; Read de Alaniz, J.; Hawker, C.J. Triazine-Mediated Controlled Radical Polymerization: New Unimolecular Initiators. Polym. Chem. 2016, 7, 370–374. [Google Scholar] [CrossRef]
- Jimenez, A.X.; Palacios, F.; de los Santos, J.M. Sc(Otf)3-Mediated [4 + 2] Annulations of N-Carbonyl Aryldiazenes with Cyclopentadiene to Construct Cinnoline Derivatives: Azo-Povarov Reaction. J. Org. Chem. 2022, 87, 11583–11592. [Google Scholar] [CrossRef] [PubMed]
- Molina, C.L.; Chow, C.P.; Shea, K.J. Type 2 Intramolecular N-Acylazo Diels-Alder Reaction: Regio- and Stereoselective Synthesis of Bridgehead Bicyclic 1,2-Diazines. J. Org. Chem. 2007, 72, 6816–6823. [Google Scholar] [CrossRef]
- Hisler, K.; Commeureuc, A.G.J.; Zhou, S.Z.; Murphy, J.A. Synthesis of Indoles via Alkylidenation of Acyl Hydrazides. Tetrahedron Lett. 2009, 50, 3290–3293. [Google Scholar] [CrossRef]
- Yuan, C.; Ning, X.J.; Gao, T.; Zeng, Z.G.; Lee, K.; Xing, Y.L.; Sun, S.F.; Wang, G.Q. [3+2] Cycloaddition of Nitrile Imines with 3-Benzylidene Succinimides: A Facile Access to Functionalized Spiropyrazolines. Asian J. Org. Chem. 2022, 11, e202100699. [Google Scholar] [CrossRef]
- Sakamoto, T.; Kikugawa, Y. Synthesis of N-Phenylalkanehydrazonoyl Chlorides. Chem. Pharm. Bull. 1988, 36, 800–802. [Google Scholar] [CrossRef]
- Yamaguchi, J.I.; Aoyagi, T.; Fujikura, R.; Suyama, T. An Oxidative Transformation of N′-Phenylhydrazide to T-Butyl Ester Using a Copper (II) Halide-Lithium T-Butoxide System. Chem. Lett. 2001, 30, 466–467. [Google Scholar] [CrossRef]
- Lopez, R.R.; Romero, G.R.; Ortega, C.E.; Garrido, F.A. Dissipation Studies of Famoxadone in Vegetables under Greenhouse Conditions Using Liquid Chromatography Coupled to High-Resolution Mass Spectrometry: Putative Elucidation of a New Metabolite. J. Sci. Food Agric. 2019, 99, 5368–5376. [Google Scholar] [CrossRef]
- Kapkan, L.M.; Pekhtereva, T.M.; Chervinskii, A.Y.; Berdinskii, I.S. Conformation of Hydrazides. Ukr. Khim. Zh. (Russ. Ed.) 1989, 55, 404. [Google Scholar]
- Murata, T.; Hara, S.; Niizuma, S.; Hada, K.; Kawada, H.; Sakaitani, M.; Shimada, H.; Nakanishi, Y. Preparation of Quinazolinone and Isoquinolinone Derivatives as Antitumor Agents for Treating Cancer and/or Cancer Metastasis and Invasion. WO2015060373, 24 December 2015. [Google Scholar]
- Swindle, J.; Ajioka, J.; Hummel, H.S.; Robertson, S. Methods of Inhibiting Stearoyl Coa Desaturase. WO2009070533, 4 June 2009. [Google Scholar]
Compd. | R1 | R2 | C. albicans SC5314 | C. albicans 4395 | C. albicans 5122 | C. albicans 5172 | C. albicans 5272 | TAI |
---|---|---|---|---|---|---|---|---|
A1 | H | H | 26.0/>64.0 | 15.0/>64.0 | 0.9/16.0 | >64.0/>64.0 | >64.0/>64.0 | <1.76 |
A2 | 2-F | H | 13.0/64.0 | 4.1/>64.0 | 8.5/64.0 | 6.7/64.0 | 12.1/>64.0 | 1.79 |
A3 | 2-Me | H | 49.3/>64.0 | >64.0/>64.0 | 13.3/>64.0 | 21.2/>64.0 | 53.0/>64.0 | N. A.a |
A4 | 2-OMe | H | 14.7/>64.0 | 31.0/>64.0 | 5.7/>64.0 | 7.8/>64.0 | 6.4/>64.0 | 1.61 |
A5 | 2-Cl | H | 25.3/>64.0 | 52.5/>64.0 | 10.8/>64.0 | 13.8/>64.0 | 13.0/>64.0 | 1.19 |
A6 | 2-CF3 | H | 11.7/64.0 | 4.5/>64.0 | 6.3/64.0 | 12.0/64.0 | 22.1/>64.0 | 1.66 |
A7 | 2-Me&4-Cl | H | 26.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | 23.4/>64.0 | 63.0/>64.0 | N. A. |
A8 | 3-F | H | 3.4/64.0 | 9.7/16.0 | 0.7/4.0 | >64.0/>64.0 | 27.0/64.0 | N. A. |
A9 | 3-Me | H | 25.3/>64.0 | 61.4/>64.0 | 10.5/>64.0 | 14.7/>64.0 | 17.8/>64.0 | 1.13 |
A10 | 3-Cl | H | 6.9/64.0 | 6.6/>64.0 | 15.0/>64.0 | 12.3/>64.0 | 59.0/>64.0 | 1.44 |
A11 | 3-CF3 | H | 1.9/32.0 | 4.0/>64.0 | 2.8/64.0 | 7.4/>64.0 | 3.7/64.0 | 2.71 |
A12 | 3,5-diF | H | 3.6/>64.0 | 25.0/>64.0 | 1.6/8.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
A13 | 4-Me | H | 13.9/>64.0 | 31.0/>64.0 | 5.0/64.0 | 14.6/64.0 | 27.0/64.0 | 1.35 |
A14 | 4-OMe | H | 5.9/>64.0 | 32.0/>64.0 | 1.5/8.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
A15 | 4-Cl | H | 5.9/>64.0 | 32.0/>64.0 | 1.5/>64.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
A16 | 4-CN | H | 47.5/>64.0 | 15.0/>64.0 | 6.3/>64.0 | 5.8/>64.0 | 7.2/>64.0 | 1.6 |
A17 | 4-CF3 | H | >64.0/>64.0 | 15.0/>64.0 | 4.6/>64.0 | 9.6/>64.0 | 9.3/>64.0 | N. A. |
A18 | 4-Br | H | 24.4/>64.0 | >64.0/>64.0 | 7.4/>64.0 | 41.4/>64.0 | >64.0/>64.0 | N. A. |
A19 | 4-iPr | H | >64.0/>64.0 | 61.3/>64.0 | >64.0/>64.0 | >64.0/>64.0 | 13.5/>64.0 | N. A. |
A20 | 4-NO2 | H | 6.7/>64.0 | 16.0/>64.0 | 0.8/4.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
B1 | H | 2-Cl | 26.2/>64.0 | 52.3/>64.0 | 13.0/32.0 | 14.0/>64.0 | 12.5/>64.0 | 1.16 |
B2 | H | 3,5-diCl | 45.3/>64.0 | >64.0/>64.0 | 32.2/>64.0 | 45.0/>64.0 | >64.0/>64.0 | N. A. |
B3 | H | 3-Cl | 6.9/>64.0 | 19.0/>64.0 | 0.7/4.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
B4 | H | 3-CF3 | >64.0/>64.0 | >64.0/>64.0 | 31.5/>64.0 | 58.6/>64.0 | >64.0/>64.0 | N. A. |
B5 | H | 3-Br | 24.6/>64.0 | 60.0/>64.0 | 3.6/64.0 | 13.9/>64.0 | 6.3/>64.0 | 1.52 |
B6 | H | 4-I | 16.7/>64.0 | >64.0/>64.0 | 31.8/>64.0 | 30.0/>64.0 | 19.0/>64.0 | N. A. |
B7 | H | 4-Me | 13.4/>64.0 | 32.0/>64.0 | 21.5/>64.0 | 25.0/>64.0 | 13.2/>64.0 | 1.14 |
B8 | H | 4-OMe | 9.2/>64.0 | 22.0/>64.0 | 0.8/4.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
B9 | H | 4-CN | >64.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | 62.6/>64.0 | N. A. |
B10 | H | 4-CF3 | >64.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
B11 | H | 4-Cl | 10.7/>64.0 | 12.3/>64.0 | 4.8/>64.0 | 7.1/>64.0 | 57.0/>64.0 | 1.56 |
B12 | H | 4-Br | 47.5/>64.0 | 14.7/>64.0 | 50.4/>64.0 | 30.0/>64.0 | 13.1/>64.0 | 1.00 |
B13 | H | 4-iPr | 14.3/>64.0 | >64.0/>64.0 | 21.0/>64.0 | 52.7/>64.0 | >64.0/>64.0 | N. A. |
B14 | H | 4-F | 12.2/64.0 | 4.0/>64.0 | 3.5/>64.0 | 3.3/>64.0 | 14.7/>64.0 | 2.13 |
C1 | PhO | H | 31.7/>64.0 | 14.3/>64.0 | 11.0/>64.0 | 6.7/>64.0 | 7.2/>64.0 | 1.50 |
C2 | PhMe | H | 3.4/16.0 | 42.0/>64.0 | 1.7/>64.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
C3 | 2-furyl | H | 17.5/>64.0 | 45.8/>64.0 | 2.7/>64.0 | 7.3/>64.0 | 13.0/>64.0 | 1.64 |
C4 | Cyclopropyl | H | 58.9/>64.0 | 8.9/>64.0 | 7.7/>64.0 | 3.9/>64.0 | 3.8/>64.0 | 1.85 |
C5 | 1-naphthyl | H | >64.0/>64.0 | >64.0/>64.0 | 62.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | N. A. |
C6 | 2-naphthyl | H | 14.6/>64.0 | >64.0/>64.0 | 51.8/>64.0 | 58.7/>64.0 | >64.0/>64.0 | N. A. |
C7 | 2-thienyl | H | 14.2/>64.0 | 60.0/>64.0 | 7.0/>64.0 | 16.5/>64.0 | 42.0/>64.0 | 1.17 |
C8 | 3-thienyl | H | 13.9/>64.0 | 22.6/>64.0 | 11.6/>64.0 | 14.7/>64.0 | >64.0/>64.0 | N. A. |
C9 | 3-indolyl | H | >64.0/>64.0 | >64.0/>64.0 | >64.0/>64.0 | 1.4/>64.0 | >64.0/>64.0 | N. A. |
C10 | PhEt | H | 51.8/>64.0 | 16.1/>64.0 | 15.0/>64.0 | >64.0/>64.0 | 11.0/>64.0 | N. A. |
C11 | PhPr | H | >64.0/>64.0 | >64.0/>64.0 | 22.8/>64.0 | >64.0/>64.0 | 15.2/>64.0 | N. A. |
C12 | Et | H | >64.0/>64.0 | >64.0/>64.0 | 13.8/>64.0 | >64.0/>64.0 | 12.1/>64.0 | N. A. |
C13 | amyl | H | >64.0/>64.0 | 42.6/>64.0 | 34.4/>64.0 | >64.0/>64.0 | 28.5/>64.0 | N. A. |
D1 | 4-Cl | 4-F | 12.2/32.0 | 5.5/>64.0 | 6.4/>64.0 | 3.7/>64.0 | 29.5/>64.0 | 1.81 |
D2 | 3-F | 3-Cl | >64.0/>64.0 | 13.8/>64.0 | 9.6/>64.0 | >64.0/>64.0 | 7.6/>64.0 | N. A. |
D3 | 3-CF3 | 4-F | 63.6/>64.0 | >64/>64.0 | 3.8/>64.0 | >64.0/>64.0 | 7.6/>64.0 | N. A. |
D4 | 3,5-diF | 4-F | 30.4/>64.0 | 13.5/>64.0 | 6.3/>64.0 | >64.0/>64.0 | 7.6/>64.0 | N. A. |
D5 | 3,5-diF | 3-Cl | 64.0/>64.0. | 29.3/>64.0 | 2.2/>64.0 | 2.7/>64.0 | 2.4/>64.0 | 2.25 |
FLC | 1.8/16.0 | >128.0/>128.0 | 58.0/>64.0 | >64.0/>64.0 | >128.0/>128.0 | <1.19 b |
Compd. | SC5314 | 4395 | 5122 | 5172 | 5272 |
---|---|---|---|---|---|
A | 6.4 | 5.4 | 11.6 | 5.8 | 5.2 |
B | 5.0 | 4.8 | 12.0 | 4.8 | 5.0 |
C | 5.0 | 4.2 | 6.4 | 7.8 | 5.8 |
D | 3.4 | 5.8 | 9.2 | 11.2 | 7.6 |
FLC | 14.8 | <1.8 a | 2.6 | <2.6 | <1.8 a |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhu, P.; Zheng, J.; Yan, J.; Li, Z.; Li, X.; Geng, H. Design, Synthesis, and Biological Evaluation of N′-Phenylhydrazides as Potential Antifungal Agents. Int. J. Mol. Sci. 2023, 24, 15120. https://doi.org/10.3390/ijms242015120
Zhu P, Zheng J, Yan J, Li Z, Li X, Geng H. Design, Synthesis, and Biological Evaluation of N′-Phenylhydrazides as Potential Antifungal Agents. International Journal of Molecular Sciences. 2023; 24(20):15120. https://doi.org/10.3390/ijms242015120
Chicago/Turabian StyleZhu, Panpan, Jinshuo Zheng, Jin Yan, Zhaoxia Li, Xinyi Li, and Huiling Geng. 2023. "Design, Synthesis, and Biological Evaluation of N′-Phenylhydrazides as Potential Antifungal Agents" International Journal of Molecular Sciences 24, no. 20: 15120. https://doi.org/10.3390/ijms242015120