Telomerase Inhibitors from Cyanobacteria: Isolation and Synthesis of Sulfoquinovosyl Diacylglycerols from Microcystis aeruguinosa PCC 7806

• Published in: Chemistry : a European journal Vol. 19; no. 14; pp. 4596 - 4601
• Main Authors: Makhlouf Brahmi, Malika, Portmann, Cyril, D'Ambrosio, Danilo, Woods, Tom M., Banfi, Damiano, Reichenbach, Patrick, Da Silva, Laeticia, Baudat, Emilie, Turcatti, Gerardo, Lingner, Joachim, Gademann, Karl
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 02-04-2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: biological activity; Chemistry; Cyanobacteria; Derivatives; Diglycerides - chemical synthesis; Diglycerides - chemistry; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; enzymes; Fractionation; Glycolipids - chemical synthesis; Glycolipids - chemistry; Inhibition; Inhibitors; Lipids; Microcystis; Microcystis - metabolism; Phencyclidine - analogs & derivatives; structure elucidation; Structure-Activity Relationship; structure-activity relationships; Tandem Mass Spectrometry; Telomerase; Telomerase - antagonists & inhibitors; Telomerase - metabolism
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201203296

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 IC50 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.
Out in the green! Screening cyanobacteria for inhibitors of telomerase led to the identification of sulfoquinovosyl diacylglycerols as the active species (see figure). A structure–activity relationship study highlighted the importance of the lipid chains for the inhibition of telomerase, and a certain length was found to be essential for biological activity.