In vitro and ex vivo free radical scavenging activities of carazostatin, carbazomycin B and their derivatives.
Free radical scavenging activities of various carbazole compounds, carazostatin, carbazomycin B and their chemically modified derivatives were studied in vitro and ex vivo. Among these compounds, carazostatin, which was isolated as a free radical scavenger from the culture of Streptomyces chromofuscus, showed the most potent inhibitory activity against lipid peroxidation of rat brain homogenate in vitro. Carbazomycin B, a known antimicrobial antibiotic, also exhibited strong activity in this system. Although O-modified derivatives of carazostatin and carbazomycin B retained considerable activity, N,O-dimethyl derivatives did not suppress the peroxidation. On the other hand, the results from the ex vivo evaluation of these carbazoles in the lipid peroxidation system of mouse blood plasma showed that the original compounds as well as their O-modified derivatives had a strong inhibitory activity upon oral administration to mice. These findings suggest that these natural carbazoles and their effective derivatives can protect tissues from the peroxidative damage due to generation of free radicals.
Kato
S
S
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Kawasaki
T
T
Urata
T
T
Mochizuki
J
J
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D002227:Carbazoles / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers; D007408:Intestinal Absorption; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D002227:Carbazoles; D016166:Free Radical Scavengers; C063108:carazostatin; C026754:carbazomycin B