Synthesis of hydroxycoumarins and hydroxybenzo[f]- or [h]coumarins as lipid peroxidation inhibitors.
Substituted hydroxycoumarins and 7- or 8-hydroxybenzo[f]coumarins were prepared by the treatment of phenols and naphthalenediols, respectively, with malic acid and H(2)SO(4) under microwave irradiation. 7- or 8-Hydroxybenzo[f]coumarins and 6-hydroxybenzo[h]coumarin were synthesized by the reaction of naphthalenediols with ethylpropiolate in the presence of ZnCl(2) in refluxing dioxane. The compounds were tested in vitro for their ability: (i) to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (ii) to inhibit lipid peroxidation, (iii) to scavenge the superoxide anion, (iv) to inhibit the activity of soybean lipoxygenase and (v) to inhibit in vivo the carrageenin-induced rat paw edema. Most of them are potent superoxide anion scavengers and inhibit in vitro lipid peroxidation. The majority of the compounds did not show high lipoxygenase inhibitory activity. No differences were observed between biological responses of hydroxycoumarins and hydroxybenzocoumarins. Compound 3i was found to present a promising antioxidant profile.
Symeonidis
Theodoros
T
Laboratory of Organic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Chamilos
Michael
M
Hadjipavlou-Litina
Dimitra J
DJ
Kallitsakis
Michael
M
Litinas
Konstantinos E
KE
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds; D020650:Combinatorial Chemistry Techniques; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects*; D008872:Microwaves; D015394:Molecular Structure; D010851:Picrates / Q000494:pharmacology; D051381:Rats
D000975:Antioxidants; D001713:Biphenyl Compounds; D003374:Coumarins; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl