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

IF 4.3 2区医学 Q1 INFECTIOUS DISEASES

Antibiotics-Basel Pub Date : 2024-10-18 DOI:10.3390/antibiotics13100989

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

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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 Dirofilaria immitis microfilaria and/or the gastrointestinal parasite Haemonchus contortus L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of Streptomyces sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (1-10), together with the known actinopyrones A (11) and C (12). Structures for 1-12 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 D. immitis mf motility (e.g., EC₅₀ 0.05 μM for 1; EC₅₀ 2.7 μM for 5) and H. contortus L1-L3 larvae development (e.g., EC₅₀ 0.58 μM for 1; EC₅₀ 8.2 μM for 5), respectively.

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

在澳大利亚公民科学活动 "土壤促进科学"（Soil for Science）的支持下，对收集的×19 个土壤样本进行了调查，结果发现了×559 个化学去复制微生物分离物，其中×54 个对心丝虫（Dirofilaria immitis）微丝蚴和/或胃肠道寄生虫（Haemonchus contortus）L1-L3 幼虫具有显著的驱虫活性。通过化学（GNPS 和 UPLC-DAD）和培养（MATRIX）分析，对链霉菌 S4S-00196A10 进行了详细的化学研究，发现了新的抗蠕虫多酮类化合物鹅膏并吡喃酮 A-J（1-10），以及已知的放线菌酮 A（11）和 C（12）。根据详细的光谱和化学分析，确定了 1-12 的结构，初步的结构活性关系分析表明，所选的γ-吡喃酮类化合物对稻瘟病虫的作用比同分异构体α-吡喃酮类化合物强 50 倍和 13 倍以上（例如：EC50 0.05 μMf，EC50 0.05 μMf，EC50 0.05 μMf，EC50 0.05 μMf）、例如，1 的 EC50 为 0.05 μM；5 的 EC50 为 2.7 μM）和 H. contortus L1-L3 幼虫的发育（例如，1 的 EC50 为 0.58 μM；5 的 EC50 为 8.2 μM）。

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来源期刊

Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

7.30

自引率

14.60%

发文量

1547

审稿时长

11 weeks

期刊介绍： Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.