Next Article in Journal
Vitamin B Complex Treatment Attenuates Local Inflammation after Peripheral Nerve Injury
Previous Article in Journal
Polyphenol Extracts from Three Colombian Passifloras (Passion Fruits) Prevent Inflammation-Induced Barrier Dysfunction of Caco-2 Cells
Open AccessArticle

Antibacterial Isoquinoline Alkaloids from the Fungus Penicillium Spathulatum Em19

1
Department of Molecular Sciences, Uppsala BioCentrum, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden
2
Ultupharma AB, Södra Rudbecksgatan 13, SE-752 36 Uppsala, Sweden
3
Medivir AB, P.O. Box 1086, SE-141 22 Huddinge, Sweden
4
Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, P.O. Box 7036, SE-750 07 Uppsala, Sweden
5
Department of Medicinal Chemistry, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(24), 4616; https://doi.org/10.3390/molecules24244616
Received: 25 November 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 17 December 2019
(This article belongs to the Section Natural Products Chemistry)
In the search for new microbial antibacterial secondary metabolites, two new compounds (1 and 2) were isolated from culture broths of Penicillium spathulatum Em19. Structure determination by nuclear magnetic resonance and mass spectrometry identified the compounds as 6,7-dihydroxy-5,10-dihydropyrrolo[1,2-b]isoquinoline-3-carboxylic acid (1, spathullin A) and 5,10-dihydropyrrolo[1,2-b]isoquinoline-6,7-diol (2, spathullin B). The two compounds displayed activity against both Gram-negative and -positive bacteria, including Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus. Compound 2 was more potent than 1 against all tested pathogens, with minimal inhibitory concentrations down to 1 µg/mL (5 µM) against S. aureus, but 2 was also more cytotoxic than 1 (50% inhibitory concentrations 112 and 11 µM for compounds 1 and 2, respectively, towards Huh7 cells). Based on stable isotope labelling experiments and a literature comparison, the biosynthesis of 1 was suggested to proceed from cysteine, tyrosine and methionine via a non-ribosomal peptides synthase like enzyme complex, whereas compound 2 was formed spontaneously from 1 by decarboxylation. Compound 1 was also easily oxidized to the 1,2-benzoquinone 3. Due to the instability of compound 1 and the toxicity of 2, the compounds are of low interest as possible future antibacterial drugs. View Full-Text
Keywords: antibiotic resistance; antibacterial secondary metabolites; secondary metabolism; Penicillium; isoquinoline alkaloids; dehydroalanine antibiotic resistance; antibacterial secondary metabolites; secondary metabolism; Penicillium; isoquinoline alkaloids; dehydroalanine
Show Figures

Graphical abstract

MDPI and ACS Style

Nord, C.; Levenfors, J.J.; Bjerketorp, J.; Sahlberg, C.; Guss, B.; Öberg, B.; Broberg, A. Antibacterial Isoquinoline Alkaloids from the Fungus Penicillium Spathulatum Em19. Molecules 2019, 24, 4616.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop