Telomerase inhibitors from cyanobacteria: isolation and synthesis of sulfoquinovosyl diacylglycerols from Microcystis aeruguinosa PCC 7806.
By using the Telospot assay, 27 different extracts of cyanobacteria were evaluated for telomerase inhibition. All extracts showed varying, but significant activity. We selected Microcystis aeruguinosa PCC 7806 to identify the active compound and a bioassay guided fractionation led us to isolate mixtures of sulfoquinovosyl diacylglycerols (SQDGs), which were identified by 2D NMR and MS/MS experiments. Pure SQDG derivatives were then synthesized. The IC(50) values of pure synthetic sulfoquinovosyl dipalmitoylglycerol and the monopalmitoylated derivative against telomerase were determined to be 17 and 40 μM, respectively. A structure-activity relationship study allowed the identification of compounds with modified lipophilic acyl groups that display improved activity.
Department of Chemistry, University of Basel, National Centre of Competence in Research Chemical Biology, 4056 Basel, Switzerland.
Malika
M
Makhlouf Brahmi
Cyril
C
Portmann
Danilo
D
D'Ambrosio
Tom M
TM
Woods
Damiano
D
Banfi
Patrick
P
Reichenbach
Laeticia
L
Da Silva
Emilie
E
Baudat
Gerardo
G
Turcatti
Joachim
J
Lingner
Karl
K
Gademann
D004075:Diglycerides / Q000138:chemical synthesis* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006017:Glycolipids / Q000138:chemical synthesis* / Q000737:chemistry; D046931:Microcystis / Q000378:metabolism*; D010622:Phencyclidine / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004075:Diglycerides; D004791:Enzyme Inhibitors; D006017:Glycolipids; C013694:sulfoquinovosyl diglyceride; C011993:1-piperidinocyclohexanecarbonitrile; D019098:Telomerase; D010622:Phencyclidine