The evaluation and structure-activity relationships of 2-benzoylaminobenzoic esters and their analogues as anti-inflammatory and anti-platelet aggregation agents.
Forty-seven 2-benzoylaminobenzoic esters were synthesized and evaluated in anti-platelet aggregation, inhibition of superoxide anion generation, and inhibition of neutrophil elastase release assays. Most 2-benzoylamino-4-chlorobenzoic acid derivatives showed selective inhibitory effects on arachidonic acid (AA)-induced platelet aggregation. Among them, compounds 6b and 7b exhibited more potent inhibitory effects (ca. 200-fold) than aspirin. Additionally, compounds 1a and 5a showed strong inhibitory effects on neutrophil superoxide generation with IC(50) values of 0.65 and 0.17 microM, respectively. However, compounds 6d and 6e exhibited dual inhibitory effects on platelet aggregation and neutrophil elastase (NE) release; therefore, these two compounds may be new leads for development as anti-inflammatory and anti-platelet aggregatory agents.
Hsieh
Pei-Wen
PW
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Hwang
Tsong-Long
TL
Wu
Chin-Chung
CC
Chiang
Shin-Zan
SZ
Wu
Chung-I
CI
Wu
Yang-Chang
YC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000494:pharmacology*; D004952:Esters / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000138:chemical synthesis / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001565:Benzoates; D004952:Esters; D010975:Platelet Aggregation Inhibitors; D053491:Proteinase Inhibitory Proteins, Secretory; D013481:Superoxides; D001241:Aspirin