Discovery of Natural Products and Natural Product-Like Inhibitors

天然产品--主要由微生物、真菌和无脊椎动物生物合成的小分子--具有不同的化学结构，产生广泛的生物活性，占目前使用的治疗药物的大部分。以海洋无脊椎动物为重点，我们已经确定了几类新的海洋天然产物，它们在体外有效地抑制肿瘤细胞生长和HIV-1感染。通过使用不同但互补的HIV-1检测，我们证明了咪拉巴胺，糖基化和卤化脱肽在进入早期阶段抑制HIV-1感染，并且该系列脱肽的活性谱为这类化合物提供了新的构效关系。

Natural products small molecules biosynthesized primarily by microorganisms, fungi and invertebrates - are engendered with diverse chemical structures that give rise to a broad range of biological activities and account for the majority of currently used therapeutics. With an emphasis on marine invertebrates, we have identified several classes of novel marine natural products that potently inhibit tumor cell growth in vitro, and HIV-1 infection. By employing distinct but complementary HIV-1 assays, we demonstrated that mirabamides, glycosylated and halogenated depsipeptides, inhibit HIV-1 infection at the early stage of entry, and the activity profiles for the suite of depsipeptides provided new structure activity relationships for this class of compounds.