The anti-inflammatory activity of dillapiole and some semisynthetic analogues.
BACKGROUND
Piper aduncum L. (Piperaceae) produces an essential oil (dillapiole) with great exploitative potential and it has proven effects against traditional cultures of phytopathogens, such as fungi, bacteria and mollusks, as well as analgesic action with low levels of toxicity.


OBJECTIVE
This study investigated the in vivo anti-inflammatory activity of dillapiole. Furthermore, in order to elucidate its structure-anti-inflammatory activity relationship (SAR), semisynthetic analogues were proposed by using the molecular simplification strategy.


METHODS
Dillapiole and safrole were isolated and purified using column chromatography. The semisynthetic analogues were obtained by using simple organic reactions, such as catalytic reduction and isomerization. All the analogues were purified by column chromatography and characterized by (1)H and (13)C NMR. The anti-inflammatory activities of dillapiole and its analogues were studied in carrageenan-induced rat paw edema model.


RESULTS
Dillapiole and di-hydrodillapiole significantly (p<0.05) inhibited rat paw edema. All the other substances tested, including safrole, were less powerful inhibitors with activities inferior to that of indomethacin.


CONCLUSIONS
These findings showed that dillapiole and di-hydrodillapiole have moderate anti-phlogistic properties, indicating that they can be used as prototypes for newer anti-inflammatory compounds. Structure-activity relationship studies revealed that the benzodioxole ring is important for biological activity as well as the alkyl groups in the side chain and the methoxy groups in the aromatic ring.
Center for Biological Sciences and Health, Mackenzie Presbyterian University, São Paulo, Brazil. roberto.parise@mackenzie.br
Roberto
R
Parise-Filho
Michelli
M
Pastrello
Carla Emygdio
CE
Pereira Camerlingo
Gisele Juni
GJ
Silva
Leonardo Aguiar
LA
Agostinho
Thaís
T
de Souza
Fátima Maria
FM
Motter Magri
Roberto Rodrigues
RR
Ribeiro
Carlos Alberto
CA
Brandt
Michelle Carneiro
MC
Polli
D000498:Allyl Compounds / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D002351:Carrageenan; D002845:Chromatography; D004149:Dioxoles / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D031701:Piper / Q000737:chemistry; D018515:Plant Leaves; D010938:Plant Oils / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000498:Allyl Compounds; D000893:Anti-Inflammatory Agents; D004149:Dioxoles; D010938:Plant Oils; C498255:5-allyl 6,7-dimethoxy 1,3-benzodioxole; D002351:Carrageenan; D007213:Indomethacin