Bioactive Cycloperoxides Isolated from the Puerto Rican Sponge Plakortis halichondrioides
Bioactive Cycloperoxides Isolated from the Puerto Rican Sponge Plakortis halichondrioides
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DOI：
10.1021/np100461t
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发表时间：
2010-10-01
影响因子：
5.1
通讯作者：
Jove, Richard
中科院分区：
文献类型：
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作者：
Jimenez-Romero, Carlos;Ortiz, Idelisse;Jove, Richard
从波多黎各海绵Plakortis halichondrioides中分离得到两个新的五元环聚酮内酯：表环激动酸F甲酯(1)和表环二酸(3)，以及一个过氧化氢-内酯(Plakortolide J)(2)，以及两个已报道的环过氧化氢化合物4和5。通过降解反应确定了1，2和5的绝对立体结构，然后应用Kishi方法对醇的绝对构型进行了指认。对环过氧化物1-5和半合成类似物7-12的细胞毒活性的生物筛选表明，化合物3、4和11具有很强的活性。通过抗疟疾和抗结核活性的测试，一些被测试的化合物对致病微生物恶性疟原虫和结核分枝杆菌显示出很强的活性。
Two new five-membered-ring polyketide endoperoxides, epiplakinic acid F methyl ester (1) and epiplakinidioic acid (3), and a peroxide-lactone, plakortolide J (2), were isolated from the Puerto Rican sponge Plakortis halichondrioides, along with two previously reported cyclic peroxides, 4 and 5. The structures of the new metabolites were determined by spectroscopic and chemical analyses. The absolute stereostructures of 1, 2, and 5 were determined by degradation reactions followed by application of Kishi's method for the assignment of absolute configuration of alcohols. Biological screening of cycloperoxides 1-5 and semisynthetic analogues 7-12 for cytotoxic activity against various human tumor cell lines revealed that compounds 3, 4, and 11 are very active. Upon assaying for antimalarial and antitubercular activity, some of the compounds tested showed strong activity against the pathogenic microbes Plasmodium falciparum and Mycobacterium tuberculosis.