Synthesis and biological activity evaluation of lignan lactones derived from (−)-cubebin

• Published in: Bioorganic & medicinal chemistry letters 2005-02, Vol.15 (4), p.1033-1037
• Main Authors: Silva, Rosangela da, de Souza, Gustavo H.B., da Silva, Ademar A., de Souza, Vanessa A., Pereira, Ana C., Royo, Vanesa de A., e Silva, Marcio L.A., Donate, Paulo M., de Matos Araújo, Ana L.S., Carvalho, José C.T., Bastos, Jairo K.
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics - chemical synthesis; Analgesics - pharmacology; Animals; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory and analgesic activities; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cubebin; Dose-Response Relationship, Drug; Edema - drug therapy; Lactones - chemical synthesis; Lactones - pharmacology; Lignan lactones; Lignans - chemical synthesis; Lignans - chemistry; Lignans - pharmacology; Medical sciences; Neuropharmacology; Pain Threshold - drug effects; Pharmacology. Drug treatments; Rats
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.12.035

The anti-inflammatory and analgesic activities of three dibenzylbutyrolactone lignans obtained by partial synthesis starting from (−)-cubebin ( 1), which was isolated from the seeds of Piper cubeba, were evaluated using different animal models. 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.