Synthesis and biological activity evaluation of lignan lactones derived from (-)-cubebin.
The anti-inflammatory and analgesic effects of three dibenzylbutyrolactone lignans, (-)-hinokinin (2), (-)-6,6'-dinitrohinokinin (3), and (-)-6,6'-diaminohinokinin (4), obtained by partial synthesis from (-)-cubebin (1), were investigated using different animal models. It was observed that compounds (1) and (2) inhibited the edema formation in the rat paw edema assay at the same level and that all responses were dose dependent. Also, at the dose of 30 mg/kg, compounds 1, 2, 3, and 4 inhibited the edema formation by 53%, 63%, 54%, and 82%, respectively, at the third hour of the experiment. In the acetic acid-induced writhing test in mice, compounds 2 and 4 produced inhibition levels of 97% and 92%, respectively, while 3 displayed lower effect (75%), which was still higher than 1. The assayed compounds neither displayed activity in the cell migration test nor in the hot plate test.
da Silva
Rosangela
R
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Avenida do Café, s/n(o), 14040-903 Ribeirão Preto, SP, Brazil. rosilva@usp.br
de Souza
Gustavo H B
GH
da Silva
Ademar A
AA
de Souza
Vanessa A
VA
Pereira
Ana C
AC
Royo
Vanesa de A
Vde A
E Silva
Marcio L A
ML
Donate
Paulo M
PM
de Matos Araújo
Ana L S
AL
Carvalho
José C T
JC
Bastos
Jairo K
JK
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D007783:Lactones; D017705:Lignans; C433065:cubebin