The synthesis and anti-inflammatory properties of a new sulindac analogue synthesized from natural safrole.
The synthesis of the new sulindac (3) analogue (Z)-5,6-methylenedioxy-2-methyl-1-(p-methylsulfinylbenzylidene)-3- indenyl acetic acid (1) from natural safrole (2), an abundant natural product occurring as the principal chemical constituent of Sassafraz oil, is described. The principal feature of this route is shortness, stereoselectivity, and high overall yield. The new analogue is produced in a yield of approximately 30% from the natural product. The results include the anti-inflammatory activity of 1 as well as that for its corresponding sulfide (12), a synthetic precursor of 1 that may be an important metabolic product of 1 by analogy to 3 itself. The anti-inflammatory profiles of these derivatives, measured in the carrageenan-induced rat paw edema test, indicated a 50% effective dose of 42 mg/kg for 1 and of 23 mg/kg for 12, confirming the structure-activity relationships of these agents. These results indicate that the new analogue 1 could represent a prodrug with a similar therapeutic profile to that of the pharmaceutical product 3.
Barreiro
E J
EJ
Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.
Lima
M E
ME
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D007192:Indenes / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D012451:Safrole / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007192:Indenes; D013467:Sulindac; D012451:Safrole