Protective effect and relation structure-activity of nonivamide and iododerivatives in several models of lipid oxidation.
The introduction of an iodine atom on the vanillyl moiety of nonivamide causes a switch in the vanilloid activity (TRPV1 antagonism versus TRPV1 desensitization) and nullifies the aversive properties of capsaicinoids. In the present study we investigated the effect of iodination in the vanillyl moiety on the antioxidant activity of capsaicinoids. To this aim, we have compared the protective effects of nonivamide and three iododerivatives, 2-iodononivamide (2IN), 5-iodononivamide (5IN), and 6-iodononivamide (6IN) in a series of in vitro models of lipid oxidation, namely the autoxidation and the FeCl(3)-mediated oxidation of linoleic acid at 37 degrees C and the thermal (140 degrees C), solvent-free oxidation of cholesterol. All tested compounds could protect linoleic acid and cholesterol against oxidative degradation, the order of potency being: nonivamide>5IN>6IN approximately 2IN. Our results show that, in general, the introduction of an iodine atom on the vanillyl moiety of nonivamide causes a decrease in the antioxidant activity, and this effect is sensitive to the position of iodine on the aromatic ring, with 5IN substantially retaining the efficacy of nonivamide to protect linoleic and cholesterol against free radical attack. Moreover, the pre-treatment with 5IN, at noncytotoxic concentrations, significantly preserved LDL from Cu(2+)-induced oxidative damage at 37 degrees C for 2h, inhibiting the reduction of polyunsaturated fatty acids and cholesterol and the increase of their oxidative products. The results of the present work suggest that 5IN exerts useful antioxidant properties in different in vitro systems of lipid peroxidation. This, coupled to its lacks of pungency and TRPV1 inhibiting properties, qualifies this phenolic compound as an attractive candidate for further investigations in vivo.
Rosa
Antonella
A
Dipartimento di Biologia Sperimentale, Sez. Patologia Sperimentale, Università degli Studi di Cagliari, Cagliari, Italy. anrosa@unica.it
Appendino
Giovanni
G
Melis
M Paola
MP
Deiana
Monica
M
Atzeri
Angela
A
Alessandra
Incani
I
Minassi
Alberto
A
Dessì
M Assunta
MA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D008078:Cholesterol, LDL / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D007455:Iodine / Q000737:chemistry*; D015227:Lipid Peroxidation / Q000187:drug effects*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D013552:Swine
D000975:Antioxidants; D008078:Cholesterol, LDL; D003603:Cytotoxins; D007455:Iodine; D002211:Capsaicin; C040937:nonivamide