ECO-FRIENDLY SYNTHESIS AND ANTIFUNGAL PROPERTIES OF N-SALICYLHYDRAZONES DERIVATIVES
DOI:
https://doi.org/10.31413/nat.v14i2.20347Keywords:
salicylhydrazones, Fusarium sp., Corynespora cassiicola, green synthesisAbstract
The growing demand for cleaner and more sustainable chemicals has positioned Green Synthesis as an important cornerstone of modern Organic Synthesis. In this context, N-salicylhydrazone derivatives, compounds with a broad range of pharmacological potential, were synthesized using four distinct green methodologies: magnetic stirring at room temperature, microwave-assisted reactions, ultrasound irradiation, and mechanochemistry. The synthetic routes avoided the use of toxic solvents, minimized purification steps and afforded high to excellent yields (56.64-94.07%). The chemical structures were elucidated by FT-IR and NMR spectroscopy. The antifungal activity of the derivatives was evaluated against Fusarium sp. and Corynespora cassiicola, two phytopathogens of significant agricultural relevance. Nine compounds exhibited inhibitory effects, with the 3-nitro-substituted derivative (compound 2) showing the highest % growth inhibition (33.67% for Fusarium sp. and 30.77% for C. cassiicola). The results demonstrate the potential of N-salicylhydrazones as promising chemical structures for the development of alternative antifungal agents. Overall, this study highlights the relevance of clean synthetic methodologies for the advancement of sustainable chemistry and the discovery of bioactive molecules with promising applications in crop protection.
Keywords: salicylhydrazones; Fusarium sp.; Corynespora cassiicola; green synthesis.
References
ABUZEID, H. M.; JULIEN, C. M.; ZHU, L.; HASHEM, A. M. Green synthesis of nanoparticles and their energy storage, environmental, and biomedical applications. Crystals, v. 13, n. 11, e1576, 2023. https://doi.org/10.3390/cryst13111576
ALAM, M. S.; CHOI, S.-U.; LEE, D.-U. Synthesis, anticancer, and docking studies of salicyl-hydrazone analogues: A novel series of small potent tropomyosin receptor kinase A inhibitors. Bioorganic & Medicinal Chemistry, v. 25, n. 1, p. 389-396, 2017. https://doi.org/10.1016/j.bmc.2016.11.005
ANASTAS, P. T.; WARNER, J. C. Green chemistry: theory and practice. Oxford: Oxford University Press, 2000. 152p.
BACKES, G. L.; NEUMANN, D. M.; JURSIC, B. S. Synthesis and antifungal activity of substituted salicylaldehyde hydrazones, hydrazides and sulfohydrazides. Bioorganic & Medicinal Chemistry, v. 22, n. 17, p. 4629-4636, 2014. https://doi.org/10.1016/j.bmc.2014.07.022
BELYAEVA, E. R.; MYASOEDOVA, Y. V.; ISHMURATOVA, N. M.; ISHMURATOV, G. Y. Synthesis and biological activity of N-acylhydrazones. Russian Journal of Bioorganic Chemistry, v. 48, p. 1123-1150, 2022. https://doi.org/10.1134/S1068162022060085
BOUBEKRI, Y.; SLASSI, S.; AARJANE, M.; TAZI, B.; AMINE, A. Microwave assisted synthesis, photoisomerization study and antioxidant activity of a series of N-acylhydrazones. Arabian Journal of Chemistry, v. 17, n. 9, e105913, 2024. https://doi.org/10.1016/j.arabjc.2024.105913
CUI, Z.; ITO, J.; DOHI, H.; AMEMIYA, Y.; NISHIDA, Y. Molecular design and synthesis of novel salicyl glycoconjugates as elicitors against plant diseases. Plos One, v. 9, n. 9, e108338, 2014. https://doi.org/10.1371/journal.pone.0108338
DI, Y.; CUI, X.; LIU, Y.; ZHOU, C.; REN, Y.; DI, Y.; YANG, X. Crystal structure, optical properties, and antibacterial activity of rare earth complexes with designed 2-carbonyl propionic acid-4-nitro benzoyl hydrazone. Polyhedron, v. 171, p. 571-577, 2019. https://doi.org/10.1016/j.poly.2019.07.036
FANTOZZI, N.; VOLLE, J.; PORCHEDDU, A.; VIRIEUX, D.; GARCIA, F.; COLACINO, E. Green metrics in mechanochemistry. Chemical Society Reviews, v. 52, n. 19, p. 6680-6714, 2023. https://doi.org/10.1039/D2CS00997H
GANESH, K. N.; ZHANG, D.; MILLER, S. J.; ROSSEN, K.; CHIRIK, P. J.; KOZLOWSKI, M. C.; ZIMMERMAN, J. B.; BROOKS, B. W.; SAVAGE, P. E.; ALLEN, D. T.; VOUTCHKOVA-KOSTAL, A. M. Green chemistry: a framework for a sustainable future. Organic Process Research & Development, v. 25, n. 7, p. 1455-1459, 2021. https://doi.org/10.1021/acs.oprd.1c00216
GLINMA, B.; GBAGUIDI, F. A.; KASSEHIN, U. C.; KPOVIESSI, S. D. S.; HOUNGBEME, A.; HOUNGUE, H. D.; ACCROMBESSI, G. C.; POUPAERT, J. H. Synthesis and trypanocidal activity of salicylhydrazones and p-tosylhydrazones of S-(+)-carvone and arylketones on African trypanosomiasis. Journal of Applied Pharmaceutical Science, v. 5, n. 6, p. 1-7, 2015. https://doi.org/10.7324/JAPS.2015.50601
HE, S.; CHEN, J.; YANG, R.; WU, W.; ZHAO, J.; WANG, R. Synthesis, spectrum study and biological activity of salicylaldehyde salicylhydrazone complexes with rare earth. Chinese Journal of Structural Chemistry, v. 23, p. 1387-1392, 2003.
IEQUE, A. L.; PALOMO, C. T.; SPANHOL, V. G. F.; DACOME, M. L. F. M.; PEREIRA, J. J. C.; CANDIDO, F. C.; CALEFFI-FERRACIOLI, K. R.; DIAS, V. L. S.; CARDOSO, R. F.; VANDRESEN, F.; ALVES-OLHER, V. G.; SCODRO, R. B. L. Preclinical tests for salicylhydrazones derivatives to explore their potential for new antituberculosis agents. Tuberculosis, v. 148, e102545, 2024. https://doi.org/10.1016/j.tube.2024.102545
KHARISSOVA, O. V.; KHARISOV, B. I.; OLIVA-GONZÁLEZ, C. M.; MÉNDEZ, Y. P.; LÓPEZ, I. Greener synthesis of chemical compounds and materials. Royal Society Open Science, v. 6, n. 11, e191378, 2019. http://dx.doi.org/10.1098/rsos.191378
MACHADO, I. V.; SANTOS, J. R. N.; JANUARIO, M. A. P.; CORREA, A. G. Greener organic synthetic methods: Sonochemistry and heterogeneous catalysis promoted multicomponent reactions. Ultrasonics Sonochemistry, v. 78, e105704, 2021. https://doi.org/10.1016/j.ultsonch.2021.105704
MATHEW, N.; SITHAMBARESAN, M.; KURUP, M. R. P. Spectral studies of copper(II) complexes of tridentate acylhydrazone ligands with heterocyclic compounds as coligands: X-ray crystal structure of one acylhydrazone copper(II) complex. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, v. 79, n. 5, p. 1154-1161, 2011. https://doi.org/10.1016/j.saa.2011.04.036
MENG, D.; LIU, F.; LI, Y.; YANG, Z.; LI, G.; GUO, D. Synthesis, characterization and properties of salicylhydrazide–salicylacylhydrazone derivatives and their terbium complexes. Luminescence, v. 31, p. 507-514, 2016. https://doi.org/10.1002/bio.2989
O’DONNELL, K.; ROONEY, A. P.; PROCTOR, R. H.; BROWN, D. W.; et al. Phylogenetic analyses of RPB1 and RPB2 support a middle Cretaceous origin for a clade comprising all agriculturally and medically important fusaria. Fungal Genetics and Biology, v. 52, p. 20-31, 2013. https://doi.org/10.1016/j.fgb.2012.12.004
PENG, Q.; HAO, X.; LIU, C.; LI, X.; LU, X.; LIU, X. Unveiling the resistance risk and resistance mechanism of florylpicoxamid in Corynespora cassiicola from cucumber. Pesticide Biochemistry and Physiology, v. 208, e106228, 2025. https://doi.org/10.1016/j.pestbp.2024.106228
PINHEIRO, J. C.; BATES, D. M. Mixed-effects models in S and S-PLUS. New York: Springer, 2000. 538p.
QUIROGA, E. N.; SAMPIETRO, A. R.; VATTUONE, M. A. Screening antifungal activities of selected medicinal plants. Journal of Ethnopharmacology, v. 74, p. 89-96, 2001. https://doi.org/10.1016/S0378-8741(00)00350-0
RODRIGUES, S. C.; LUCIO, K. R.; MARTINS, M. T. M.; SILVA, I. O.; MORAES, R. S. M.; DIAS, F. R. F.; CUNHA, A. L-Proline: Applications of a versatile amino acid in the areas of medicinal chemistry and organic synthesis. Revista Virtual de Química, v. 14, n. 4, p. 563-586, 2022. https://doi.org/10.21577/1984-6835.20220015
RONDON, M. N.; LAWRENCE, K. The fungal pathogen Corynespora cassiicola: a review and insights for target spot management on cotton and soya bean. Journal of Phytopathology, v. 169, n. 5, p. 245-260, 2021.
SAMPIRON, E. G.; CALSAVARA, L. L.; BALDIN, V. P.; MONTAHOLI, D. C.; LEME, A. L. D.; NAMBA, D. Y.; ALVES-OLHER, V. G.; CALEFFI-FERRACIOLLI, K. R.; CARDOSO, R. F.; SIQUEIRA, V. L. D.; VANDRESEN, F.; SCODRO, R. B. L. Isoniazid-N-acylhydrazones as promising compounds for the anti-tuberculosis treatment. Tuberculosis, v. 141, e102363, 2023. https://doi.org/10.1016/j.tube.2023.102363
SIMIJONOVIĆ, D. M.; MILENKOVIĆ, D. A.; AVDOVIĆ, E. H.; MILANOVIĆ, Ž. B.; ANTONIJEVIĆ, M. R.; AMIĆ, A.; DOLIĆANIN, Z.; MARKOVIĆ, Z. S. Coumarin N-acylhydrazone derivatives: Green synthesis and antioxidant potential - Experimental and theoretical study. Antioxidants, v. 12, e1858, 2023. https://doi.org/10.3390/antiox12101858
SZKLARZEWICZ, J.; JUROWSKA, A.; HODOROWICZ, M.; et al. Characterization and antidiabetic activity of salicylhydrazone Schiff base vanadium(IV) and (V) complexes. Transition Metal Chemistry, v. 46, p. 201-217, 2021. https://doi.org/10.1007/s11243-020-00437-1
SUN, J.; YANG, X. Q.; WAN, J. L.; HAN, H. L.; ZHAO, Y. D.; CAI, L.; YANG, Y.-B.; DING, Z. T. The antifungal metabolites isolated from maize endophytic fungus Fusarium sp. induced by OSMAC strategy. Fitoterapia, v. 171, e105710, 2023. https://doi.org/10.1016/j.fitote.2023.105710
VALVERDE, T. L.; SAMPIRON, E. G.; MONTAHOLI, D. C.; BALDIN, V. P.; INSAURRALDE, D. D.; ALVES-OLHER, V. G.; SIQUEIRA, V. L.; CALEFFI-FERRACIOLI, K. R.; CARDOSO, R. F.; VANDRESEN, F.; SCODRO, R. B. L. 3,5-dinitrobenzoylhydrazone derivatives as a scaffold for antituberculosis drug development. Future Microbiology, v. 17, p. 267-280, 2022. https://doi.org/10.2217/fmb-2021-0119
XIAO, M.; YE, J.; LIAN, W.; et al. Microwave-assisted synthesis, characterization and bioassay of acylhydrazone derivatives as influenza neuraminidase inhibitors. Medicinal Chemistry Research, v. 26, p. 3216-3227, 2017. https://doi.org/10.1007/s00044-017-2015-6
ZHAO, Z. X.; CHENG, L. P.; PANG, W. Tetrahedron Letters, v. 59, p. 2079-2081, 2018. https://doi.org/10.1016/j.tetlet.2018.04.047
Downloads
Published
Issue
Section
How to Cite
License
Copyright (c) 2026 Nativa
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright for articles published in this journal are the authors, with first publication rights granted to the journal. The journal shows open access, and articles are free to use, with proper attribution, in educational and non-commercial.
The articles published in this journal may be reproduced in part or used as a reference by other authors, provided that the source is quoted.
