Abstract
In view of the growing spread of antibiotic resistant bacteria causing high morbidity and mortality, it is essential to develop compounds that are more efficient than those currently on the market. Maleimide derivatives, due to their chemical structure, have biological activity capable of deactivating enzymes and inhibiting the metabolic pathway of these bacteria and fungi. They have high selectivity and are new excellent antimicrobials. In this scenario, the objective of this work was to synthesize, characterize and verify the existence of bactericidal activity of two derivatives of maleimides, 4-vinyl-phenyl-maleimide and Cl-phenyl- maleimide. For this, the structures of the two compounds were characterized by High Resolution Mass Spectrometry (HRMS), Infrared (IR) and Nuclear Magnetic Resonance (NMR) 1H. Both compounds showed a double bond in the maleimide ring, essential for the inhibition of enzymes present in bacteria. The disk diffusion test to determine the bactericidal activity of the compounds, was carried out against the microorganisms: S. Aureus (Staphylococcus Aureus)—Gram positive, Monocytosis Lister—Gram positive, Escherichia Coli Enteropathogenic (EPEC)—Gram negative and Pseudomones Aureginosas—Gram negative. Compounds derived from maleimide obtain greater biological activity in Gram positive microorganisms, as evidenced by the inhibition halo in the diffusion test. The compounds proved to be active in the face of the disk diffusion test, indicating new permeability, selectivity and mechanistic studies, as well as possible applications of them as bactericidal agents.
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References
Tacconelli E, Carrara E, Savoldi A et al (2018) Discovery, research, and development of new antibiotics: the who priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18(3):318–272. https://doi.org/10.1016/s1473-3099(17)30753-3
Butler M, Blaskovich M, Cooper M (2016) Antibiotics in the clinical pipeline at the end of 2015. Springer Science and Business Media LLC 70(1):3–24. https://doi.org/10.1038/ja.2016.72
Salewska N, Boros-Majewska J, Lcka I et al (2012) Chemical reactivity and antimicrobial activity of n-substituted maleimides. J Enzyme Inhib Med Chem 70(1):117–124. https://doi.org/10.17576/mjas-2016-2004-06
Bansode T, Shelke J, Dongre G (2009) Synthesis and antimicrobial activity of some new n-acyl substituted phenothiazines. Eur J Med Chem 44(12):5094–5098. https://doi.org/10.1016/j.ejmech.2009.07.006
Prado S, Cechinel-Filho V, Campos-Buzzi F et al (2004) Biological evaluation of some selected cyclic imides: mitochondrial effects and in vitro cytotoxicity. Zeitschrift Fur Naturforschung Sect C J Biosci 59(9–10):663–672
Ye X, Li X, Yuan L et al (2007) Interaction of houttuyfonate homologues with the cell membrane of gram-positive and gram-negative bacteria. Colloids Surf Physicochem Eng Aspects 301(1–3):412–418. https://doi.org/10.1016/j.colsurfa.2007.01.012
Xu H, Baidoo K, Wong K et al (2008) A novel bifunctional maleimido chx-a″ chelator for conjugation to thiol-containing biomolecules. Bioorg Med Chem Lett 18(8):2679–2683. https://doi.org/10.1016/j.bmcl.2008.03.022
Chen X, Zhang L, Li F et al (2015) Synthesis and antifungal evaluation of a series of maleimides. Pest Manag Sci 71(3):433–440. https://doi.org/10.1002/ps.3824
Silvia N, Maria, V (2005) In vitro antifungal properties, structure-activity relationships and studies on the mode of action of N-phenyl, N-aryl, N-phenylalkyl maleimides and related compounds. Arzneim-Forsch 123–132.
Fan Y, Lu Y, Chen X et al (2018) Anti-leishmanial and cytotoxic activities of a series of maleimides: synthesis biological evaluation and structure-activity relationship. Molecules 23(11):2878–2887. https://doi.org/10.3390/molecules23112878
Hassan N (2016) Synthesis and antimicrobial activities of eleven N-substituted maleimides. Malaysian J Anal Sci 20:741–750. https://doi.org/10.17576/mjas-2016-2004-06
Weinstein M, Patel J, Burnham C et al (2018) Performance standards for antimicrobial disk tests. 9th ed. CLSI approved standard M2–A9, Pennsylvania, USA 15–39
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Trindade, A.C., Uchoa, A.F. (2022). Synthesis of N-substituted Maleimides Potential Bactericide. In: Bastos-Filho, T.F., de Oliveira Caldeira, E.M., Frizera-Neto, A. (eds) XXVII Brazilian Congress on Biomedical Engineering. CBEB 2020. IFMBE Proceedings, vol 83. Springer, Cham. https://doi.org/10.1007/978-3-030-70601-2_157
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DOI: https://doi.org/10.1007/978-3-030-70601-2_157
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