Synthesis and antinociceptive activity of capsinoid derivatives

• Published in: European journal of medicinal chemistry Vol. 44; no. 8; pp. 3345 - 3349
• Main Authors: He, G.-J., Ye, X.-L., Mou, X., Chen, Z., Li, X.-G.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.08.2009; Elsevier
• Subjects: Analgesics; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - pharmacology; Animals; Antinociceptive activity; Biological and medical sciences; Capsaicin; Capsinoid; Capsinoid derivatives; Chemistry, Medicinal; Drug Design; Esters - chemical synthesis; Esters - chemistry; Esters - pharmacology; Female; Life Sciences & Biomedicine; Male; Medical sciences; Mice; Neuropharmacology; Nonpungency; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Structure-Activity Relationship; Antinociceptive activity; C.L; Nonpungency; Capsinoid derivatives; RPP; Capsaicin; Capsinoid; MPP; Chain length; Organoleptic properties; Rodentia; Indometacin; Biological activity; Vertebrata; Mammalia; Analgesic; Mouse; Animal; Pungency; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.02.017

According to the data of structural identification, six capsinoids or their derivatives were successfully synthesized to test for their analgesic activity. Three of them were capsinoids with different acyl chain compared with capsaicin after substitution of ester for amide at C 1 position. The other three could be described as capsinoid derivatives with different alkoxy chain, compared with capsaicin after substitution of ester for amide at C 1 position and alkoxy for hydroxy at C 4 position and synthesis of them was reported first. Compared with capsaicin, experiment results about pungency showed that capsinoids and their derivatives synthesized were all no or only slight pungent; that is, capsinoid derivates synthesized still have the same advantage of nonpungency with capsinoid. Relation between analgesic activity and molecular structure of compounds synthesized was also reported first, which would facilitate finding capsinoid derivatives owning excellent analgesic activity. The experiment results about analgesic activity showed that capsinoids displayed moderate analgesia effect and their antinociceptive activity decreased with the elongation of acyl chain at C 1 position; that antinociceptive activities of capsinoid derivatives synthesized were much stronger not only than those of indomethacin but also than those of their precursor (vanillyl decanoate), which increased with elongation of alkoxyl chain at C 4 position. Especially 4-hexyloxyl-3-methoxybenzyl decanoate showed the best antinociceptive activity in synthesized compounds, which was 9-fold higher than its precursor (vanillyl decanoate) and 6-fold higher than that of indomethacin. [Display omitted] Two group homologues (capsinoid group and capsinoid derivate group) were synthesized to evaluate for their analgesic activity. Synthesis of capsinoid derivate group was reported first. And the relationship between analgesic activity and molecular structure of two group homologues synthesized was also reported first, which would facilitate finding capsinoid derivative owning excellent analgesic activity.