Goondolinones A and B: Terpenyl-quinolin-4(1H)-ones from an Australian Volcanic Crater Soil-Derived Actinomadura sp., with Selective Activity against Dirofilaria immitis (Heartworm).

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2024-11-24 DOI:10.1021/acs.jnatprod.4c01146

Jianying Han, David F Bruhn, Dana C Roberts, Erica J Burkman, Yovany Moreno, Paul V Bernhardt, Angela A Salim, Robert J Capon

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引用次数: 0

Abstract

A chemical investigation of the Australian pasture soil-derived Actinomadura sp. S4S-00245B09, supported by chemical, bioactivity and cultivation profiling, yielded a new class of terpenyl-quinolin-4(1H)-ones, goondolinones A and B (1 and 2), featuring an unprecedented fused seven-membered ether. Structures were assigned to 1 and 2 on the basis of detailed spectroscopic analysis, including X-ray analysis of 1, and biosynthetic considerations. Goondolinone A (1) lacks antibacterial or antifungal properties, is noncytotoxic to two human carcinoma cell lines, but exhibits selective inhibition of the motility of heartworm Dirofilaria immitis microfilaria (EC₅₀ 5.1 μM) and L4 larvae (EC₅₀ 21.4 μM). As a new anthelmintic scaffold, future understanding of the structure activity relationship and mechanism of action of 1 could inform the discovery of new treatments for heartworm and other filarial diseases, capable of safeguarding the health and welfare of companion animals.

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Goondolinones A and B: Terpenyl-quinolin-4(1H)-ones from an Australian Volcanic Crater Soil-Derived Actinomadura sp.

在化学、生物活性和培养剖面分析的支持下，对澳大利亚牧场土壤衍生的放线菌（Actinomadura sp. S4S-00245B09）进行了化学研究，发现了一类新的三萜类喹啉-4(1H)-酮--鹅掌楸酮 A 和 B（1 和 2），其特点是前所未有的融合七元醚。根据详细的光谱分析（包括 1 的 X 射线分析）和生物合成方面的考虑，确定了 1 和 2 的结构。鹅掌楸内酯 A（1）缺乏抗菌或抗真菌特性，对两种人类癌细胞株无细胞毒性，但对心丝虫微丝蚴（EC50 5.1 μM）和 L4 幼虫（EC50 21.4 μM）的蠕动具有选择性抑制作用。作为一种新的抗蠕虫药支架，未来对 1 的结构活性关系和作用机制的了解可为发现心丝虫和其他丝虫疾病的新疗法提供依据，从而保障伴侣动物的健康和福利。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.