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Cylindrofridins A–C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale

Author:
Preisitsch, Michael, Niedermeyer, Timo H. J., Heiden, Stefan E., Neidhardt, Inga, Kumpfmüller, Jana, Wurster, Martina, Harmrolfs, Kirsten, Wiesner, Christoph, Enke, Heike, Müller, Rolf, Mundt, Sabine
Source:
Journal of natural products 2016 v.79 no.1 pp. 106-115
ISSN:
1520-6025
Subject:
Cyanobacterium (genus), Cylindrospermum stagnale, Nostoc, Streptococcus pneumoniae, alkylresorcinols, antibiotic resistance, biomass, carbon, chlorination, high performance liquid chromatography, inhibitory concentration 50, methicillin, methicillin-resistant Staphylococcus aureus, minimum inhibitory concentration, nuclear magnetic resonance spectroscopy, screening, solvents, toxicity
Abstract:
A rapid and exhaustive one-step biomass extraction as well as an enrichment and cleanup procedure has been developed for HPLC-UV detection and quantification of closely related [7.7]paracyclophanes and structural derivatives based on a two-phase solvent system. The procedure has been validated using the biomass of the carbamidocyclophane- and cylindrocyclophane-producing cyanobacterium Nostoc sp. CAVN2 and was utilized to perform a screening comprising 102 cyanobacterial strains. As a result, three new cylindrocyclophane-related alkylresorcinols, cylindrofridins A–C (1–3), and known cylindrocyclophanes (4–6) were detected and isolated from Cylindrospermum stagnale PCC 7417. Structures of 1–3 were elucidated by a combination of 1D and 2D NMR experiments, HRMS, and ECD spectroscopy. Cylindrofridin A (1) is the first naturally occurring [7.7]paracyclophane-related monomeric derivative. In contrast, cylindrofridins B (2) and C (3) represent dimers related to 1. Due to chlorination at the alkyl carbon atom in 1–3, the site of [7.7]paracyclophane macrocycle formation, the cylindrofridins represent linearized congeners of the cylindrocyclophanes. Compounds 1–3 were not toxic against nontumorigenic HaCaT cells (IC₅₀ values >25 μM) compared to the respective cylindrocyclophanes, but 1 was the only cylindrofridin showing moderate activity against methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae with MIC values of 9 and 17 μM, respectively.
Agid:
5498360