Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
O mercado de cosmético passa por uma tendência em empregar filtros solares de origem natural em formulações fotoprotetoras, seja isolado ou como adjuvantes de filtros sintéticos. O açafrão-da-terra (Curcuma longa) teve o seu valor medicinal reconhecido pelo SUS no ano de 2009, sendo incluído da RENISUS. Assim, a mistura curcuminoide (MC) foi extraída e modificada para gerar a MCA. As chalconas (CH e CHA) foram planejadas considerando a estrutura molecular do metoxicinamato de octila, um filtro solar comercial, e da MC. Os métodos in vitro de Mansur e Diffey foram usados para determinar o fator de proteção solar (FPS-UVB) e o comprimento de onda crítico (λc) das formulações contendo os compostos em estudo. A MC, a MCA, a CH e a CHA mostraram os seguintes valores de FPS-UVB e λc (nm): MC (0,9 e 394), MCA (5,2 e 391), CH (5,4 e 388) e CHA (11,6 e 358). Os resultados indicam que os compostos têm potencial para atuarem conferindo proteção contra a radiação UVB e/ou UVA. Dentre os filtros químicos avaliados, a CHA demonstrou potencial para atuar como filtro UV de amplo espectro, exibindo efeito fotoprotetor comparável ao da oxibenzona (FPS 11,3 e λc 348 nm), filtro químico comercial.
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