Synthesis and pharmacochemical evaluation of novel aryl-acetic acid inhibitors of lipoxygenase, antioxidants, and anti-inflammatory agents.
Lipoxygenase catalyzes the first two steps of the transformation of arachidonic acid into leukotrienes which are implicated in host defense reactions. It is well known that many acids possess potent anti-inflammatory activity. Taking into account that compounds bearing a thienyl, naphthyl, pyrollyl, and 2,4-di-tert-butyl-phenol moieties possess anti-inflammatory activity which is related to their capacity to transfer electrons and to scavenge reactive oxygen species, we synthesized some new aryl-acetic acids and we explored their ability to inhibit soybean lipoxygenase, to present antioxidant and anti-inflammatory activities, and to interact with glutathione. The compounds have shown important antioxidant activity, medium anti-inflammatory activity, and very good inhibition of soybean lipoxygenase. Compound 3-(3,5-di-tert-butyl-2-hydroxy-phenyl)-2-phenyl-acrylic acid (1i) showed significant in vitro LO inhibition (IC(50) 65 microM). The results are discussed in terms of structural and physicochemical characteristics of the compounds. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity are experimentally determined by RPTLC method.
Pontiki
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Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Hadjipavlou-Litina
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D019342:Acetic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism*; D002351:Carrageenan / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005609:Free Radicals / Q000737:chemistry; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005609:Free Radicals; D016859:Lipoxygenase Inhibitors; D002351:Carrageenan; D019342:Acetic Acid