EVALUATION OF NEW SESQUITERPENE QUINONES FROM 2 DYSIDEA SPONGE SPECIES AS INHIBITORS OF PROTEIN TYROSINE KINASE
EVALUATION OF NEW SESQUITERPENE QUINONES FROM 2 DYSIDEA SPONGE SPECIES AS INHIBITORS OF PROTEIN TYROSINE KINASE
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DOI：
10.1021/jo00050a043
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发表时间：
1992-11-20
影响因子：
3.6
通讯作者：
MORETTI, R
中科院分区：
文献类型：
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作者：
ALVI, KA;DIAZ, MC;MORETTI, R
我们发现被认为在肿瘤发生中起重要作用的酶的抑制剂的计划推动了一项研究，即从海绵中提取的倍半萜类化合物(氢醌)对抗pp60v-src蛋白酪氨酸激酶(PTK)。从海绵中分离得到5个新的代谢物，分别为蜜环酮A(3)、蜜环酮B(4)、18-甲氧基瓦酮(6a)、波洛瓦酮-C(8)和波洛环酮-D(9)。这些化合物还伴随着两个已知的化合物，(+)-香豆素(2a)和(+)-19-甲氧基香酮(7)。所有这些化合物都具有连接到含有额外杂原子的苯醌部分的4，9-呋喃甲醚阵列。通过光谱分析确定了新化合物的结构，并测试了所有化合物对pp60V-src PTK的抑制活性。化合物4的IC50几乎等于28微米，被认为对该酶具有中等活性。其他化合物都没有活性。
Our program to discover inhibitors of enzymes thought to be important in tumorigenesis motivated a study of marme sponge-derived sesquiterpene quinones (hydroquinones) against pp60v-src protein tyrosine kinase (PTK). Five new metabolites were isolated from the sponge Dysidea avara including melemeleone A (3), melemeleone B (4),18-methoxyavarone (6a), popolohuanone-C (8), and popolohuanone-D (9). These were accompanied by two known compounds, (+)-avarol (2a) and (+)-19-methoxyavarone (7). All of these compounds possess a 4,9-friedodrimane array linked to a quinone moiety containing additional heteroatoms. The new structures were determined from analysis of spectroscopic data, and all compounds were tested for inhibitory activity against pp60v-src PTK. Compound 4 had an IC50 of almost-equal-to 28 muM and was considered to be moderately active against this enzyme. The other compounds were all inactive.