Keywords
How to Cite
Abstract
The insecticidal potential of 4-aminoantipyrine derivatives remain underexplored despite their broad scientific applications. To develop safer insecticides for stored grain protection, a series of 4-aminoantipyrine Schiff bases were synthesized and characterized using FTIR, UV-Vis, EI-MS, and ¹H NMR spectroscopy. Insecticidal activity against Tribolium castaneum, Sitophilus oryzae, and Rhyzopertha dominica was evaluated via the impregnated filter paper method. Cytotoxicity was assessed using the brine shrimp lethality test. Chemical reactivity descriptors were obtained through Density Functional Theory (DFT), while binding affinities and receptor interactions were investigated using molecular docking simulations with two target receptors. Compounds D, F, and M exhibited excellent insecticidal activity against Rhyzopertha dominica at 239.5 µg/cm², while H and K showed moderate effects. None of the synthesized compounds showed activity against Tribolium castaneum or Sitophilus oryzae. All the synthesized compounds were non-cytotoxic to regular cell lines. These findings highlight D, F, and M as promising leads for the development of next-generation grain storage pesticides.
References
Akbari, Z.; Stagno, C.; Iraci, N.; Efferth, T.; Omer, E. A.; Piperno, A.; Micale, N. Biological evaluation, DFT, MEP, HOMO-LUMO analysis and ensemble docking studies of Zn (II) complexes of bidentate and tetradentate Schiff base ligands as antileukemia agents. Journal of Molecular Structure, 2024, 1301, 137400. https://doi.org/10.1016/j.molstruc.2023.137400
Banti, C. N.; Hadjikakou, S. K. Evaluation of Toxicity with Brine Shrimp Assay. Bio-prot. 2021, 11 (2), e3895. https://doi.org/10.21769/BioProtoc.3895
Becke, A. D. Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 1993, 98, 5648–5652. https://doi.org/10.1063/1.464913
Dissanayaka, D. M. S. K.; Sammani, A. M. P.; Wijayaratne, L. K. W.; Rajapakse, R. H. S.; Hettiarachchi, S, Morrison W. R. Effects of aggregation pheromone concentration and distance on the trapping of Rhyzopertha dominica (Coleoptera: Bostrychidae) adults. J. Stored. Prod. Res. 2020, 88, 1–10. https://doi.org/10.1016/j.jspr.2020.101657
Erazua, E. A.; Adeleke, B. B. DFT and Molecular Docking Investigation of Potential Anticancer Properties of Some Flavonoids. J. Pure Appl. Chem. 2019, 8 (3), 225–231. https://doi.org/10.21776/ub.jpacr.2019.008.03.485
Erazua, E. A.; Oyebamiji, A. K.; Adeleke, B. B. DFT-QSAR and Molecular Docking Studies on 1,2,3-Triazole-Dithiocarbamate Hybrids as Potential Anticancer Agents. Phys. Sci. Int. 2019, 4, 1–10. https://doi.org/10.26538/tjnpr/v5i11.22
Erazua, E. A.; Adepoju, A. J.; Ajayi, A. P.; Josiah, O. M.; Akintelu, S. A; Oyebamiji, A. K. Theoretical Studies on Triazoles of 3-Acetylbetulin and Betulone as Anticancer Agents. Nat and Sci. 2021, 19 (7), 5–18. https://doi.org/10.7537/marsnsj190721.02
Erazua, E. A.; Oyebamiji, A. K.; Akintelu, S. A.; Adewole, P. D.; Adelakun, A.; Adeleke, B. B. Quantitative Structure-Activity relationship, Molecular Docking and ADMET Screening of Tetrahydroquinoline Derivatives as Anti-Small Cell Lung Cancer Agents. Eclét. Quím. 2023, 48 (1), 55–71. https://doi.org/10.26850/1678-4618eqj.v48.1.2023.p55-71
Erazua, E. A.; Adeleke, B. B. Antioxidant, anti-inflammatory and anti-glycation activities of some 4-aminoantypyrine derivatives: In vitro and in silico study. JOPAT. 2024, 23 (1), 1313–1347. https://doi.org/10.4314/jopat.v23i1.9
Erazua, E. A; Olaseinde, A. A; Oyebamiji, A. K; Oluwakemi, E.; Adekunle, D.; Olanrewaju, A. A. Molecular docking and ADMET profiling of Carbazole-rhodanine hybrid as anticancer agent. JOPAT. 2024, 23 (2), 1491–1515. https://doi.org/10.4314/jopat.v23i2.8
Gareau, B. J. Lessons from the Montreal Protocol delay in phasing out methyl bromide. J. Environ. Sci. Stud. 2015, 5 (2), 163–168. https://doi.org/10.1007/s13412-014-0212-x
Ghorab, M. M.; El-Gazzar, M. G.; Alsaid, M. S. Synthesis, Characterization and Anti-Breast Cancer Activity of New 4-Aminoantipyrine-Based Heterocycles. Int. J. Mol. Sci. 2014, 15, 539–553. https://doi.org/10.3390/ijms15057539
Grewal, A. S.; Singla, A.; Kamboj, P.; Dua, J. S.; Pesticide residues in food grains, vegetables, and fruits: a hazard to human health. J. Med. Chem. and Tox. 2017, 2 (1), 40–46. https://doi.org/10.15436/2575-808X.17.1355
Halim, K. N. M.; Ramadan, S. K.; Rizk, S. A.; El-Hashash, M. A. Synthesis, DFT study, molecular docking, and insecticidal evaluation of some pyrazole-based tetrahydropyramimidine derivatives. Synth. Commun. 2020, 50 (8), 1159–1175. https://doi.org/10.1080/00397911.2020.1720739
Herrera, J. M.; Pizzolitto, R. P.; Zunino, M. P, Dambolena, J. S.; Zygadlo, J. A. Effect of fungal volatile organic compounds on a fungus and an insect that damage stored maize. J Stored Prod Res. 2015, 62, 74–80. https://doi.org/10.1016/j.jspr.2015.04.006
Huang, D.; Liu, A.; Liu, W.; Liu, X.; Ren, Y.; Zheng, X. Synthesis and insecticidal activities of novel 1H-pyrazole-5-carboxylic acid derivatives. Heterocycl Commun. 2012, 23 (6), 455–460. https://doi.org/10.1515/hc-2017-0110
Kashyap, S.; Kumar, S.; Ramasamy, K.; Lim, S. M.; Shah, S. A; Narasimhan, B. Synthesis, biological evaluation, and corrosion inhibition studies of transition metal complexes of Schiff base. Chem. Cent. J. 2018, 12, 117. https://doi.org/10.1186/s13065-018-0487-1
Kaya, K.Y.; Yilmaz, V. T.; and Buyukgungor, O. Synthesis, Spectroscopic, Structural and Quantum Chemical Studies of a New Imine Oxime and Its Palladium (II) Complex: Hydrolysis Mechanism. Molecules. 2016, 21 (1), 52. https://doi.org/10.3390/molecules21010052
Khan, S. A.; Ranjha, M. H.; Khan, A. A; Sagheer, M.; Abbas, A.; Hassan, Z.; Insecticidal efficacy of wild medicinal plants, Dhutura alba and Calotropis procera, against Trogoderma granarium (Everts) in wheat store grains. Pak. J. Zoo. 2019, 51 (1), 289–294. https://doi.org/10.17582/journal.pjz/2019.51.1.289.294
Kim, M.; Sim, C.; Shin, D.; Suh, E.; Cho, K. Residual and Sublethal Effects of Fenpyroximate and Pyridaben on the Instantaneous Rate of Increase of Tetranychus Urticae. Crop Prot. 2006, 25, 542–548. https://doi.org/10.1016/j.cropro.2005.08.010
Lampiri, E.; Agrafioti, P; Levizou, E.; Athanassiou, C. G.; Insecticidal effect of Dittrichia viscosa lyophilized epicuticular material against four major stored-product beetle species on wheat. Crop Prot. 2019, 132, 105–119. https://doi.org/10.1016/j.cropro.2020.105095
Marcic, D. Sublethal Effects of Tebufenpyrad on the Eggs and Immatures of Two-Spotted Spider Mite, Tetranychus Urticae. Exp. Appl. Acarol. 2005, 36, 177–185. https://doi.org/10.1007/s10493-005-3579-2
Matsuzaka, Y.; Uesawa, Y. Computational Models That Use a Quantitative Structure-Activity Relationship Approach Based on Deep Learning. Processes. 2023, 11, 1296. https://doi.org/10.3390/pr11041296
Murtaza, S.; Akhtar, M. S.; Kanwal, F.; Abbas, A.; Ashiq S.; Shamim S. Synthesis and biological evaluation of schiff bases of 4-aminophenazone as anti-inflammatory, analgesic and antipyretic agent. J. Saudi Chem. Soc. 2017, 21, S359–S372. https://doi.org/10.1016/j.jscs.2014.04.003
Neggaz, S.; Chenni, M.; Zitouni-Haouar, F. E.; Fernandez, X. Mycochemical composition and insecticidal bioactivity of Algerian desert truffles extract against two stored-product insects: Sitophilus oryzae (L.) (Coleoptera: Curculionidae) and Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae). Biotech. 2010, 10 (11), 481. https://doi.org/10.1007/s13205-020-02472-2
Nonaka, N. Tolfenpyrad-A New Insecticide with Wide Spectrum and Unique Action. Agrochem Jpn. 2003, 83, 17–19.
Nopsa, J. F. H.; Daglish, G. J.; Hagstrum, D. W.; Leslie, J. F.; Phillips, T. W.; Scoglio, C.; Thomas-Sharma, S.; Walter, G. H.; Garret, K. A. Ecological Networks in Stored Grain: Key Postharvest Nodes for Emerging Pests, Pathogens, and Mycotoxins. Biosci. 2015, 65, 985–1002. https://doi.org/10.1093/biosci/biv122
Oyebamiji, K. A.; Semire, B. Studies of 1, 4-Dihydropyridine Derivatives for Anti-Breast Cancer (MCF-7) Activities: Combinations of DFT-QSAR and Docking Methods. N. Y. Sci. J. 2016, 9 (6), 58–66. https://doi.org/10.7537/marsnys09061610
Raman, N.; Selvan, A.; Manisankar, P. Spectral, magnetic, biocidal screening, DNA binding and photocleavage studies of mononuclear Cu (II) and Zn (II) metal complexes of tricoordinate heterocyclic Schiff base ligands of pyrazolone and semicarbazide/thiosemicarbazide based derivatives. Spectrochim. Acta – A. 2017, 76, 161–173. https://doi.org/10.1016/j.saa.2010.03.007
Raza, M.A.; Mumtaz, M.W.; Ozturk, S.; Latif, M.; Aisha; Ashraf, A.; Dege, N.; Dogan, O.E.; Agar, E.; Rehman, S.U.; et al. Experimental and Theoretical Biological Probing of Schiff Bases as Esterase Inhibitors: Structural, Spectral and Molecular Insights. Molecules 2023, 28, 5703. https://doi.org/10.3390/molecules28155703
Rouhani, M.; Samih, M.A.; Gorji, M.; Moradi, B. H. Insecticidal effect of plant extracts on common Pistachio psylla, Agonoscena pistaciae Burckhardt and lauterer (Hemiptera: Aphalaridae). Arch. Phytopathol. Plant Prot. 2019, 52 (1–2), 45–53. https://doi.org/10.1080/03235408.2019.1570589
Sabaa, M. W.; Mohamed, N. A; Mohamed, R. R.; Khalil, K. M.; Latif, S. M. Synthesis, Characterization and Antimicrobial Activity of Poly (N-Vinyl imidazole) Grafted Carboxymethyl Chitosan. Carbohydr. Polym. 2010, 79, 998–1005. https://doi.org/10.1016/j.carbpol.2009.10.024
Selby, T. P.; Lahm, G. P.; Stevenson, T. M.; Hughes, K. A; Cordova, D; Annan, I. B. Discovery of Cyantraniliprole, a Potent and Selective Anthranilic Diamide Ryanodine Receptor Activator with Cross-Spectrum Insecticidal Activity. Bioorg. Med. Chem. Lett. 2013, 23, 6341–6345. https://doi.org/10.1016/j.bmcl.2013.09.076
Singh, G.; Satija, P.; Singh, B.; Sinha, S.; Sehgal, R.; Sahoo, S. C. Design, crystal structures and sustainable synthesis of family of antipyrine derivatives: Abolish to bacterial and parasitic infection. J. Mol. Struct. 2020, 1199, 127010. https://doi.org/10.1016/j.molstruc.2019.127010
Song, H.; Liu, Y.; Xiong, L.; Li, Y.; Yang, N.; Wang, Q. Design, Synthesis, and Insecticidal Activity of Novel Pyrazole Derivatives Containing α-Hydroxymethyl-N-benzyl Carboxamide, α-Chloromethyl-N-benzyl Carboxamide, and 4,5-Dihydrooxazole Moieties. J. Agric. Food Chem. 2012, 60, 1470–1479. https://doi.org/10.1021/jf204778v
Suryawanshi, V. S.; Yadav, A. R; Mohite, S. K.; Magdum, C. S. Toxicological Assessment using Brine Shrimp Lethality Assay and Antimicrobial activity of Capparis Grandis. Shanghai Ligong Daxue Xuebao. 2020, 22 (11), 746–759.
Suthisut, D.; Fields, P. G.; Chandrapatya, A. Fumigant toxicity of essential oils from three Thai plants (Zingiberaceae) and their major compounds against Sitophilus zeamais, Tribolium castaneum and two parasitoids. J Stored Prod Res. 2011, 47, 222–230. https://doi.org/10.1016/j.jspr.2011.03.002
Teran, R.; Guevara, R.; Mora, J.; Dobronski, L.; Barreiro-Costa, O; Beske. Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine. Mol. 2019, 24 (15), 2696. https://doi.org/10.3390/molecules24152696
Trott, O.; Olson, A. J; AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization and Multithreading. J. Comput. Chem. 2010, 31, 455–461. https://doi.org/10.1002/jcc.21334
Yaman, C.; Simsek, S. Insecticidal effect from three Hypericum species extracts against Rhyzopertha dominica, Sitophilus oryzae and Tribolium confusum. Ciência e Agrotecnologia. 2021, 45, e001921. https://doi.org/10.1590/1413-7054202145001921
Yang, L.; Feng, J.; Ren, A. Theoretical studies on the electronic and optical properties of two thiophene–fluorene based π-conjugated copolymers. Polym. J. 2005, 46, 10970–10982. https://doi.org/10.1016/j.polymer.2005.09.050
Yu, H.; Xu, M.; Cheng, Y.; Wu, H.; Luo, Y.; Li, B. Synthesis and Acaricidal Activity of Cyenopyrafen and Its Geometric Isomer. Arkivoc. 2012, VI, 26–34. https://doi.org/10.3998/ark.5550190.0013.603
Yusuf, T. L.; Oladipo, S. D.; Olagboye, S. A; Zamisa, S. J.; Tolufashe, G. F. Solvent-free synthesis of nitrobenzyl Schiff bases: Characterization, antibacterial studies, density functional theory and molecular docking studies. Journal of Molecular Structure. 2020, 1222: 128857. https://doi.org/10.1016/j.molstruc.2020.128857
Zaater, S.; Bouchoucha, A.; Djebbar, S.; Brahimi, M. Structure, vibrational analysis, electronic properties, and chemical reactivity of two benzoxazole derivatives: functional density theory study. J. Mol. Struct. 2016, 1123, 344–354. https://doi.org/10.1016/j.molstruc.2016.06.047
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2026 Eclética Química