Natural Products from Microalgae with Potential against Alzheimer's Disease: Sulfolipids Are Potent Glutaminyl Cyclase Inhibitors.
In recent years, many new enzymes, like glutaminyl cyclase (QC), could be associated with pathophysiological processes and represent targets for many diseases, so that enzyme-inhibiting properties of natural substances are becoming increasingly important. In different studies, the pathophysiology connection of QC to various diseases including Alzheimer's disease (AD) was described. Algae are known for the ability to synthesize complex and highly-diverse compounds with specific enzyme inhibition properties. Therefore, we screened different algae species for the presence of QC inhibiting metabolites using a new "Reverse Metabolomics" technique including an Activity-correlation Analysis (AcorA), which is based on the correlation of bioactivities to mass spectral data with the aid of mathematic informatics deconvolution. Thus, three QC inhibiting compounds from microalgae belonging to the family of sulfolipids were identified. The compounds showed a QC inhibition of 81% and 76% at concentrations of 0.25 mg/mL and 0.025 mg/mL, respectively. Thus, for the first time, sulfolipids are identified as QC inhibiting compounds and possess substructures with the required pharmacophore qualities. They represent a new lead structure for QC inhibitors.
Group Algae Biotechnology, Department of Applied Biosciences and Process Technology, Anhalt University of Applied Sciences, 06366 Köthen, Germany. stephanie.hielscher-michael@hs-anhalt.de.|Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, 06120 Halle (Saale), Germany. stephanie.hielscher-michael@hs-anhalt.de.
Stephanie
S
Hielscher-Michael
Group Algae Biotechnology, Department of Applied Biosciences and Process Technology, Anhalt University of Applied Sciences, 06366 Köthen, Germany. carola.griehl@hs-anhalt.de.
Carola
C
Griehl
Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, 06120 Halle (Saale), Germany. mirko.buchholz@izi.fraunhofer.de.
Mirko
M
Buchholz
Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, 06120 Halle (Saale), Germany. hans-ulrich.demuth@izi.fraunhofer.de.
Hans-Ulrich
HU
Demuth
Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, 06120 Halle (Saale), Germany. Norbert.Arnold@ipb-halle.de.
Norbert
N
Arnold
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, 06120 Halle (Saale), Germany. wessjohann@ipb-halle.de.
Ludger A
LA
Wessjohann
D000544:Alzheimer Disease / Q000188:drug therapy*; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000502:physiology*; D058086:Microalgae / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001688:Biological Products; D004791:Enzyme Inhibitors; D008055:Lipids; C015518:sulfolipids; D019881:Aminoacyltransferases; C059280:glutaminyl-peptide cyclotransferase
AD; Scenedesmus sp.; glutaminyl cyclase (QC) inhibitor; microalgae; natural product; reverse metabolomics; sulfolipids