Improved anti-inflammatory activity of three new terpenoids derived, by systematic chemical modifications, from the abundant triterpenes of the flowery plant Calendula officinalis.
Rings A, D and E of faradiol (1), and ring E of both arnidiol (10) and calenduladiol (4) have been subjected to various selective chemical manipulations to modify polarity, water affinity, H-bonding, sterics, and number of aromatic groups of these anti-inflammatory natural compounds. A total of 15 new and four known pentacyclic triterpenoids have been obtained in this way. Some 13 terpenoids were evaluated for their topical anti-inflammatory activities with respect to inhibition of croton oil induced ear oedema in mouse. Three derivatives of 1, the C(16) benzyl ether 15, the C(30) aldehyde 24, and the C(30) primary alcohol 25 showed significantly improved anti-inflammatory potencies, which is relevant for (future) structure-activity-relationship (SAR) studies.
Neukirch
Hannes
H
Laboratorio di Chimica Bioorganica, Università di Trento, Via Sommarive 14, I-38050 Povo-Trento.
D'Ambrosio
Michele
M
Sosa
Silvio
S
Altinier
Gianmario
G
Della Loggia
Roberto
R
Guerriero
Antonio
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D020838:Calendula / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D035264:Flowers / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013729:Terpenes