NOVEL CYTOTOXIC TOPOISOMERASE-II INHIBITING PYRROLOIMINOQUINONES FROM FIJIAN SPONGES OF THE GENUS ZYZZYA
NOVEL CYTOTOXIC TOPOISOMERASE-II INHIBITING PYRROLOIMINOQUINONES FROM FIJIAN SPONGES OF THE GENUS ZYZZYA
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DOI：
10.1021/ja00058a003
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发表时间：
1993-03-10
影响因子：
15
通讯作者：
IRELAND, CM
中科院分区：
文献类型：
--
作者：
RADISKY, DC;RADISKY, ES;IRELAND, CM
我们从斐济海绵Zyzzya cf. marsailis中分离并鉴定了7个新的[天然]吡咯亚胺醌，makaluvamines A- f (1-6), makaluvone(7)以及已知化合物discorhabdin A(8)和damirone B(9)。makaluvamines在体外对人结肠癌细胞系HCT 116表现出强大的细胞毒性，对拓扑异构酶II敏感的CHO细胞系xrs-6表现出不同的毒性，并在体外抑制拓扑异构酶II。这种活性可能通过插入DNA和单链断裂介导。马卡鲁vamine A和C对人卵巢癌Ovcar3植入胸腺小鼠显示出体内抗肿瘤活性。makaluvamines表明batzelline/ isobatelline和discorhabdin/prianosin类化合物之间存在一种合理的相互关系。
We present the isolation and characterization of seven novel [natural] pyrroloiminoquinones, the makaluvamines A-F (1-6), makaluvone (7), and the known compounds discorhabdin A (8) and damirone B (9) from the Fijian sponge Zyzzya cf. marsailis. The makaluvamines exhibit potent in vitro cytotoxicity toward the human colon tumor cell-line HCT 116, show differential toxicity toward the topoisomerase II sensitive CHO cell-line xrs-6, and inhibit topoisomerase II in vitro. This activity may be mediated by intercalation into DNA and single-stranded breakage. Makaluvamine A and C exhibited in vivo antitumor activity against the human ovarian carcinoma Ovcar3 implanted in athymic mice. The makaluvamines suggest a plausible interrelationship between the batzelline/isobatzelline and discorhabdin/prianosin classes of compounds.