Abstract
Diabetes is a disease linked to pathologies, such as chronic inflammation, neuropathy, and pain. The synthesis by the Claisen−Schmidt condensation reaction aims to obtain medium to high yield chalconic derivatives. Studies for the synthesis of new chalcone molecules aim at the structural manipulation of aromatic rings, as well as the replacement of rings by heterocycles, and combination through chemical reactions of synthesized structures with other molecules, in order to enhance biological activity. A chalcone was synthesized and evaluated for its antinociceptive, anti-inflammatory and hypoglycemic effect in adult zebrafish. In addition to reducing nociceptive behavior, chalcone (40 mg/kg) reversed post-treatment-induced acute and chronic hyperglycemia and reduced carrageenan-induced abdominal edema in zebrafish. It also showed an inhibitory effect on NO production in J774A.1 cells. When compared with the control groups, the oxidative stress generated after chronic hyperglycemia and after induction of abdominal edema was significantly reduced by chalcone. Molecular docking simulations of chalcone with Cox -1, Cox-2, and TRPA1 channel enzymes were performed and indicated that chalcone has a higher affinity for the COX-1 enzyme and 4 interactions with the TRPA1 channel. Chalcone also showed good pharmacokinetic properties as assessed by ADMET.
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The Universidade Estadual do Ceará-UECE, Fundação de Amparo à Pesquisa do Estado do Ceará (FUNCAP), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and the CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for financial support and scholarship. Helcio Silva dos Santos acknowledges financial support from CNPq (Grant 306008/2022-0), Maria Kueirislene Amancio Ferreira acknowledges financial support from PDPG-POSDOC/Programa de Desenvolvimento da Pós-Graduação (PDPG) Pós-Doutorado Estratégico S (Grant 88881.692120/2022-01).
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Ferreira, M.K.A., Freitas, W.P.O., Barbosa, I.M. et al. Heterocyclic chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(thiophen-2-yl) prop-2-en-1-one derived from a natural product with antinociceptive, anti-inflammatory, and hypoglycemic effect in adult zebrafish. 3 Biotech 13, 276 (2023). https://doi.org/10.1007/s13205-023-03696-8
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DOI: https://doi.org/10.1007/s13205-023-03696-8