FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139
AbstractThe rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 µM, which was more efficient than thrombin inhibition of EC50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF) and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors. View Full-Text
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Anas, A.R.J.; Mori, A.; Tone, M.; Naruse, C.; Nakajima, A.; Asukabe, H.; Takaya, Y.; Imanishi, S.Y.; Nishizawa, T.; Shirai, M.; Harada, K.-I. FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139. Mar. Drugs 2017, 15, 275.
Anas ARJ, Mori A, Tone M, Naruse C, Nakajima A, Asukabe H, Takaya Y, Imanishi SY, Nishizawa T, Shirai M, Harada K-I. FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139. Marine Drugs. 2017; 15(9):275.Chicago/Turabian Style
Anas, Andrea R.J.; Mori, Akane; Tone, Mineka; Naruse, Chiaki; Nakajima, Anna; Asukabe, Hirohiko; Takaya, Yoshiaki; Imanishi, Susumu Y.; Nishizawa, Tomoyasu; Shirai, Makoto; Harada, Ken-ichi. 2017. "FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139." Mar. Drugs 15, no. 9: 275.
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