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

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.

Automated summary

The synthesis of new chalcone molecules aims to enhance biological activity through structural manipulation of aromatic rings and combination with other molecules. A synthesized chalcone showed antinociceptive, anti-inflammatory, and hypoglycemic effects in zebrafish. It also reduced oxidative stress and had high affinity for COX-1 and TRPA1 enzymes.