Syntheses of 5,7,8- and 5,6,7-trioxygenated 3-alkyl-3',4'-dihydroxyflavones and their inhibitory activities against arachidonate 5-lipoxygenase.

5,6,7- and 5,7,8-Trioxygenated 3',4'-dihydroxyflavones were derivatized by introducing alkyl groups of various chain lengths at the 3-position of the flavone skeleton. These compounds were tested as inhibitors for arachidonate 5-lipoxygenase purified from porcine leukocytes. Modification of the 3-position with an alkyl group of 6-10 carbons markedly decreased the IC50 values. 3-Hexyl-3',4'-dihydroxy-5,7, 8-trimethoxyflavone inhibited 5-lipoxygenase with an IC50 value of 58 nM. The platelet and leukocyte 12-lipoxygenases, 15-lipoxygenase of reticulocytes, and cyclooxygenase of vesicular gland were inhibited less potently (IC50 = 0.4, 0.4, 2.7, and 30 microM). Thus, the compound was a relatively selective inhibitor for 5-lipoxygenase.