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臺灣三種海洋細菌之生物活性成分研究 • 以三種不同培養基篩選出143株海洋細菌株，經醱酵培養後，萃取液初步以抑制一氧化氮合成酶 (NOS) 的活性與利用Phenylephrine誘發大鼠 (Sprague-Dawley Rat) 胸主動脈收縮活性平台進行篩選出具有抑制血管收縮的菌株。結果自143株海洋菌株萃取液中發現二株對於RAW 264.7細胞具有細胞毒性，分別為 Streptomyces sp. (#HYC21) 和 Pseudoalteromonas sp. (#HYC13)，另一株 Pseudomonas aeruginosa (#M1B) 則具有抑制血管收縮的活性，後續針對這三株具有生物活性的菌株以PPY、PY和PYG 培養基分批擴大培養，進行一系列的分析、分離、純化與構造解析，計分離、決定出二十一個化合物，包括：二個環肽類抗生素 (cyclic peptide antibiotics) 的actinomycin X2 (1)、actinomycin D (2)；二個多溴酚類抗生素 (polybrominated phenolic antibiotics) 的 pentabromopseudilin (8) 和3,3′,5,5′-tetrabromo-2,2′-biphenyldiol (9)；三個膽酸及其類似物 (cholic acid and its analogs) 的cholic acid (10)、deoxycholic acid (11)、glycocholic acid (12)；五個喹啉生物鹼 (quinoline alkaloid) 分別為2- heptylquinol-4-one (13)、2-heptyl-3-hydroxyquinolin-4(1H)-one (14)、2-(1′E-nonenyl)quinol-4-one (15)、2-nonylquinol-4-one (16)、 3-heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione (17)；二個酚類化合物 (phenolics) 的2-(2-hydroxyphenyl)-2-thiazoline-4-methanol (18)、4,4′-isopropylidenebisphenol (19)；一個吩嗪生物鹼 (phenazine alkaloid) phenazine-1-carboxamide (21) 及五個環化雙胺基酸 (diketopiperazine) 分別為cyclo-L-Pro-L-Val (3)、cyclo-L-Pro-L-Ile (4)、cyclo-L-Pro-L-Leu (5)、cyclo-D-Pro-L-Phe (6)、cyclo-L-Pro-L-Phe (7)、cyclo-L-Pro-L-Trp (20)。此外，由M1B所分離得到的化合物在生物活性及作用機制，刻正持續探究中。
Studies on the bioactive constituents of three marine bacterial species isolated in Taiwan • In this study, 143 strains of marine bacteria isolated from Taiwan were cultured for the screening of their inducible nitric oxide synthase (iNOS) inhibitory activity and vasorelaxing activity. Of these bacterial strains monitored, HYC21 (Streptomyces sp.) and HYC13 (Pseudoalteromonas sp.) exhibited cytotoxic activities against RAW 264.7 cell line. While M1B (Pseudomonas aeruginosa) exhibited vasorelaxing activity on Sprague-Dawley rats induced by phenylephrine. Based on these findings, the three strains were thus mass cultured and a series of separation and isolation were undertaken to investigate their active principles. Totally twenty-one compounds including 2 cyclic peptide antibiotics, 2 polybrominated phenolic antibiotics, 3 cholic acid and its analogs, 5 quinoline alkaloids, 2 phenolics, a phenazine alkaloid, and 6 diketopiperazine was isolated and identified. Their structures were elucidated to be actinomycin X2 (1), actinomycin D (2), cyclo-L-Pro-L-Val (3), cyclo-L-Pro-L-Ile (4), cyclo-L-Pro-L-Leu (5), cyclo-D-Pro-L-Phe (6), cyclo-L-Pro-L-Phe (7), pentabromopseudilin (8), 3,3′,5,5′-tetrabromo-2,2′-biphenyldiol (9), cholic acid (10), deoxycholic acid (11), glycocholic acid (12), 2-heptylquinol-4-one (13), 2-heptyl-3-hydroxyquinolin-4(1H)-one (14), 2- (1′E-nonenyl)quinol-4-one (15), 2-nonylquinol-4-one (16), 3- heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione (17), 2-(2-hydroxyphenyl)-2-thiazoline-4-methanol (18), 4,4′-isopropylidenebisphenol (19), cyclo-L-Pro-L-Trp (20), phenazine-1-carboxamide (21).
