Analgesic and anti-inflammatory activities evaluation of (-)-O-acetyl, (-)-O-methyl, (-)-O-dimethylethylamine cubebin and their preparation from (-)-cubebin.
The anti-inflammatory and antinociceptive effects of the acetylated (2), methylated (3) and aminated (4) derivatives of cubebin (1), obtained by its reaction with acetic anhydride, methyl iodide and dimethylethylamine chloride, respectively, were investigated, using different animal models. The compound (2) was the most effective anti-inflammatory one in the carrageenin-induced paw edema in rats and was the only one which showed dose-response correlation for this assay with r = 0.993 and Y = 64.58x + 0.22. Besides, compounds (2) and (4) were more effective than cubebin in inhibiting acetic acid-induced writhing in mice, producing dose-response correlation with doses of 10, 20 and 30 mg/kg, respectively. Regarding the hot plate and the cell migration tests in rats, none of the four tested compounds showed activity. Overall, the results showed that the acetylation and amination of cubebin were efficient in enhancing its analgesic activity, as well as its anti-inflammatory activity.
Souza
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GH
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Cafe S/N, Ribeirão Preto, 14040 903, São Paulo, Brazil.
da Silva Filho
A A
AA
de Souza
V A
VA
Pereira
A C
AC
Royo
V de A
Vde A
e Silva
M L A
ML
da Silva
R
R
Donate
P M
PM
Carvalho
J C T
JC
Bastos
J K
JK
D019342:Acetic Acid / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D002351:Carrageenan / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004149:Dioxoles / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology*; D017705:Lignans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004149:Dioxoles; D005663:Furans; D017705:Lignans; C489938:O-acetyl cubebin; C489939:O-dimethylethylamine cubebin; D002351:Carrageenan; C433065:cubebin; D019342:Acetic Acid