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A novel series of thromboxane A2 synthetase inhibitors with free radical scavenging and anti-peroxidative activities

A novel series of indoline derivatives with imidazole and carboxyl moieties were synthesized and evaluated for their thromboxane A2 (TXA2) synthetase inhibiting, radical scavenging and anti-peroxidative activities. Among the compounds synthesized, 3.{5-substituted-3-[2-(imidazol-1-yl)ethyl]indolin-1-yl}propionic acids showed free radical scavenging activity and inhibitory effects on lipid-peroxidation of rat brain homogenate and on arachidonate-induced TXA2-dependent aggregation of rabbit platelets. The anti-platelet and anti-peroxidative activities were related to the lipophilicity of the 5-substituent. The 5-hexyloxy derivative (13) showed about 35-fold higher inhibitory activity on TXA2 synthesis than that of ozagrel and about 100-fold higher activity on lipid peroxidation than that of alpha-tocopherol. Compound 13 showed in vivo anti-thrombotic effect in mice and ex vivo anti-peroxidative activity in rats.

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Reference£º
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles