Goondicones A–H: Spiro-Isoindolinone Heartworm Anthelmintics from an Australian Pasture-Soil-Derived Streptomyces sp. DOI Creative Commons
Jianying Han,

David F. Bruhn,

Cynthia T. Childs

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(12), P. 1222 - 1222

Published: Dec. 17, 2024

Background/Objectives: There is an urgent need for new and improved anthelmintics that are not constrained by existing resistance pathways can safeguard the health welfare of animals. Methods: An integrated platform chemical, bioassay, cultivation profiling applied to a library microbes isolated from Australian livestock pasture soil was used detect guide production, isolation, characterization, identification, evaluation natural products with anthelmintic properties. Results: A global social (GNPS) molecular network analysis 110 pasture-soil-derived microbial extracts prioritized antiparasitic activity identified unique families in extract Streptomyces sp. S4S-00185A06, strain selectively active against Dirofilaria immitis microfilariae. UPLC-DAD metabolites UV-vis chromophores unprecedented formulas. chemical investigation S4S-00185A06 yielded goondicones A–H (1–8) as examples rare class spiro-isoindolinones, structures assigned on basis detailed spectroscopic analysis, ECD calculations, biosynthetic considerations. Conclusions: While 1–8 exhibit little no vitro inhibitory Gram-positive, Gram-negative, and/or fungal pathogens, human carcinoma cells, or gastrointestinal parasite Haemonchus contortus L1–L3 larvae, 5 6 (and, lesser extent, 1) inhibit motility heartworm microfilaria (IC50 10–11 μM). structure relationship based co-metabolites suggests (i) 8-OH preferable 8–oxo moiety, (ii) 20-NMe 3-OH moieties essential, (iii) C-9 epimerization exerts discernible impact potency.

Language: Английский

Hot off the press DOI
Robert A. Hill, Andrew Sutherland

Natural Product Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

A personal selection of 32 recent papers is presented covering various aspects current developments in bioorganic chemistry and novel natural products, such as hyperzrone from Hypericum beanii .

Language: Английский

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0
Goondicones A–H: Spiro-Isoindolinone Heartworm Anthelmintics from an Australian Pasture-Soil-Derived Streptomyces sp. DOI Creative Commons
Jianying Han,

David F. Bruhn,

Cynthia T. Childs

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(12), P. 1222 - 1222

Published: Dec. 17, 2024

Background/Objectives: There is an urgent need for new and improved anthelmintics that are not constrained by existing resistance pathways can safeguard the health welfare of animals. Methods: An integrated platform chemical, bioassay, cultivation profiling applied to a library microbes isolated from Australian livestock pasture soil was used detect guide production, isolation, characterization, identification, evaluation natural products with anthelmintic properties. Results: A global social (GNPS) molecular network analysis 110 pasture-soil-derived microbial extracts prioritized antiparasitic activity identified unique families in extract Streptomyces sp. S4S-00185A06, strain selectively active against Dirofilaria immitis microfilariae. UPLC-DAD metabolites UV-vis chromophores unprecedented formulas. chemical investigation S4S-00185A06 yielded goondicones A–H (1–8) as examples rare class spiro-isoindolinones, structures assigned on basis detailed spectroscopic analysis, ECD calculations, biosynthetic considerations. Conclusions: While 1–8 exhibit little no vitro inhibitory Gram-positive, Gram-negative, and/or fungal pathogens, human carcinoma cells, or gastrointestinal parasite Haemonchus contortus L1–L3 larvae, 5 6 (and, lesser extent, 1) inhibit motility heartworm microfilaria (IC50 10–11 μM). structure relationship based co-metabolites suggests (i) 8-OH preferable 8–oxo moiety, (ii) 20-NMe 3-OH moieties essential, (iii) C-9 epimerization exerts discernible impact potency.

Language: Английский

Citations

0