Structure-activity relationships of vanillic acid ester analogs in inhibitory effect of antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells.
Methyl vanillate (1) showed strong degranulation inhibitory activity among vanillin derivatives tested. In order to find structure-activity relationships for developing anti-allergic agents with simple structures and potent activity, we synthesized several vanillic acid (VA) ester derivatives with C1-C4 and C8 alkyl chains and evaluated their degranulation inhibitory activities. The most active compound of VA ester derivatives was derivative 5 with a C4 straight alkyl chain, and derivative 5 exhibited approximately three-fold greater inhibitory activity than that of 1. Moreover, we designed 8 types of analogs based on 5, and we found that the minimum structure for potent degranulation inhibitory activity requires direct connection of the butyl ester moiety on the benzene ring and at least one hydroxyl group on the benzene ring. Butyl meta or para hydroxyl benzoate (10 or 11) has a simpler structure than that of 5 and exhibited more potent degranulation inhibitory activity than that of 5.
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
Nao
N
Ishimata
Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
Hideyuki
H
Ito
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan. Electronic address: atai@pu-hiroshima.ac.jp.
Akihiro
A
Tai
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015471:Leukemia, Basophilic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D014641:Vanillic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000941:Antigens; D004952:Esters; D014641:Vanillic Acid
Degranulation; RBL-2H3; Structure–activity relationships; Vanillic acid ester