贡达吡喃酮A-J：源自澳大利亚土壤的一种菌种产生的聚酮类α和γ吡喃酮驱虫剂

Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived sp.

作者信息

Jin Shengbin, Bruhn David F, Childs Cynthia T, Burkman Erica, Moreno Yovany, Salim Angela A, Khalil Zeinab G, Capon Robert J

机构信息

Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.

Boehringer Ingelheim Animal Health, USA Inc., 1730 Olympic Drive, Athens, GA 30601, USA.

出版信息

Antibiotics (Basel). 2024 Oct 18;13(10):989. doi: 10.3390/antibiotics13100989.

DOI:10.3390/antibiotics13100989

PMID:39452255

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11505385/

Abstract

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm microfilaria and/or the gastrointestinal parasite L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (-), together with the known actinopyrones A () and C (). Structures for - were assigned on the basis of detailed spectroscopic and chemical analysis, with preliminary structure activity relationship analysis revealing selected γ-pyrones >50-fold and >13-fold more potent than isomeric α-pyrones against mf motility (e.g., EC 0.05 μM for ; EC 2.7 μM for ) and L1-L3 larvae development (e.g., EC 0.58 μM for ; EC 8.2 μM for ), respectively.

摘要

在澳大利亚公民科学倡议项目“科学土壤”的支持下，对采集的19份土壤样本进行调查，共获得559种经化学去重复的微生物分离物，其中54种对犬心丝虫微丝蚴和/或胃肠道寄生虫L1 - L3幼虫表现出显著的驱虫活性。化学分析（GNPS和UPLC - DAD）及培养分析（MATRIX）促使对菌株S4S - 00196A10进行详细的化学研究，从中得到了新的驱虫聚酮化合物贡达吡喃酮A - J（-），以及已知的放线吡喃酮A（）和C（）。通过详细的光谱和化学分析确定了-的结构，初步的构效关系分析表明，所选的γ - 吡喃酮对微丝蚴活力的活性比异构体α - 吡喃酮高50倍以上和13倍以上（例如，对的EC为0.05 μM；对的EC为2.7 μM），对L1 - L3幼虫发育的活性分别为（例如，对的EC为0.58 μM；对的EC为8.2 μM）。