TY - JOUR
T1 - Cylindrofridins A-C, Linear Cylindrocyclophane-Related Alkylresorcinols from the Cyanobacterium Cylindrospermum stagnale
AU - Preisitsch, M.
AU - Niedermeyer, T.H.J.
AU - Heiden, S.E.
AU - Neidhardt, I.
AU - Kumpfmüller, J.
AU - Wurster, M.
AU - Harmrolfs, K.
AU - Wiesner, C.
AU - Enke, H.
AU - Müller, R.
AU - Mundt, S.
N1 - Publisher Copyright:
© 2015 The American Chemical Society and American Society of Pharmacognosy.
PY - 2015/12/18
Y1 - 2015/12/18
N2 - 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 (IC
50 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.
AB - 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 (IC
50 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.
KW - antibiotic agent
KW - carbon
KW - cyclophane derivative
KW - cylindrocyclophane derivative
KW - cylindrofridin A
KW - cylindrofridin B
KW - cylindrofridin C
KW - cytotoxic agent
KW - macrocyclic compound
KW - resorcinol derivative
KW - unclassified drug
KW - antibacterial activity
KW - antibiotic sensitivity
KW - Article
KW - chlorination
KW - cyanobacterium
KW - Cylindrospermum stagnale
KW - cytotoxicity
KW - experiment
KW - halogenation
KW - heteronuclear multiple bond correlation
KW - heteronuclear single quantum coherence
KW - hydrophilicity
KW - IC50
KW - Klebsiella pneumoniae
KW - limit of detection
KW - limit of quantitation
KW - methicillin-resistant Staphylococcus epidermidis
KW - microbial biomass
KW - minimum inhibitory concentration
KW - nonhuman
KW - proton nuclear magnetic resonance
KW - Pseudomonas aeruginosa
KW - reversed phase high performance liquid chromatography
KW - Streptococcus pneumoniae
KW - ultraviolet spectrophotometry
KW - chemical structure
KW - chemistry
KW - drug effects
KW - isolation and purification
KW - methicillin resistant Staphylococcus aureus
KW - microbial sensitivity test
KW - nuclear magnetic resonance
KW - structure activity relation
KW - Cyanobacteria
KW - Methicillin-Resistant Staphylococcus aureus
KW - Microbial Sensitivity Tests
KW - Molecular Structure
KW - Nuclear Magnetic Resonance
KW - Biomolecular
KW - Resorcinols
KW - Structure-Activity Relationship
UR - http://www.scopus.com/inward/record.url?scp=84956670818&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.5b00768
DO - 10.1021/acs.jnatprod.5b00768
M3 - Article
SN - 0163-3864
VL - 79
SP - 106
EP - 115
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 1
ER -