Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Department of Chemistry, University of South Florida, Tampa, FL, USA.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):1404-1410. doi: 10.1080/14756366.2022.2078320.
Nature has been always a great source of possible lead compounds to develop new drugs against several diseases. Here we report the identification of a natural compound, membranoid G, derived from the Antarctic sponge displaying an inhibitory activity against human DNA topoisomerase 1B. The experiments indicate that membranoid G, when pre-incubated with the enzyme, strongly and irreversibly inhibits the relaxation of supercoiled DNA. This compound completely inhibits the cleavage step of the enzyme catalytic mechanism by preventing protein binding to the DNA. Membranoid G displays also a cytotoxic effect on tumour cell lines, suggesting its use as a possible lead compound to develop new anticancer drugs.
大自然一直是开发新药物对抗多种疾病的潜在先导化合物的重要来源。在这里，我们报告了一种天然化合物 membranoid G 的鉴定，它来源于南极海绵，对人源拓扑异构酶 1B 具有抑制活性。实验表明，membranoid G 与酶预孵育时，强烈且不可逆地抑制超螺旋 DNA 的松弛。该化合物通过阻止蛋白质与 DNA 结合，完全抑制酶催化机制的切割步骤。Membranoid G 对肿瘤细胞系也表现出细胞毒性作用，提示其可作为开发新型抗癌药物的潜在先导化合物。
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