Han Jianying, Bruhn David F, Roberts Dana C, Burkman Erica J, Moreno Yovany, Bernhardt Paul V, Salim Angela A, Capon Robert J
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
Boehringer Ingelheim Animal Health, USA Inc., 1730 Olympic Drive, Athens Georgia 30601, United States.
J Nat Prod. 2024 Dec 27;87(12):2855-2862. doi: 10.1021/acs.jnatprod.4c01146. Epub 2024 Nov 24.
A chemical investigation of the Australian pasture soil-derived sp. S4S-00245B09, supported by chemical, bioactivity and cultivation profiling, yielded a new class of terpenyl-quinolin-4(1)-ones, goondolinones A and B ( and ), featuring an unprecedented fused seven-membered ether. Structures were assigned to and on the basis of detailed spectroscopic analysis, including X-ray analysis of , and biosynthetic considerations. Goondolinone A () lacks antibacterial or antifungal properties, is noncytotoxic to two human carcinoma cell lines, but exhibits selective inhibition of the motility of heartworm microfilaria (EC 5.1 μM) and L4 larvae (EC 21.4 μM). As a new anthelmintic scaffold, future understanding of the structure activity relationship and mechanism of action of could inform the discovery of new treatments for heartworm and other filarial diseases, capable of safeguarding the health and welfare of companion animals.
对源自澳大利亚牧场土壤的菌株S4S - 00245B09进行化学研究，并辅以化学、生物活性和培养分析，得到了一类新的萜烯基喹啉 - 4(1) - 酮，即贡多林酮A和B（ 和 ），其具有前所未有的稠合七元醚结构。基于详细的光谱分析（包括对 的X射线分析）和生物合成方面的考虑，确定了 和 的结构。贡多林酮A（ ）没有抗菌或抗真菌特性，对两种人类癌细胞系无细胞毒性，但对犬恶丝虫微丝蚴（EC 5.1 μM）和L4幼虫（EC 21.4 μM）的运动表现出选择性抑制作用。作为一种新的驱虫支架，未来对 的构效关系和作用机制的了解可能会为发现治疗犬恶丝虫和其他丝虫病的新疗法提供信息，从而保障伴侣动物的健康和福祉。
