Polyoxometalates as potent inhibitors for acetyl and butyrylcholinesterases and as potential drugs for the treatment of Alzheimer’s disease
- 831 Downloads
Polyoxometalates (POMs) show significant importance in medicine due to their enzyme inhibition, antiviral and anticancer properties. In this study, some polyoxotungstates were identified as potent inhibitors of acetyl and butyrylcholinesterases. Compounds [H2W12O42]10− and [TeW6O24]6− have the most potent acetylcholinesterase activity, exhibiting IC50 values of 0.29 ± 0.01 and 0.31 ± 0.01 μM, respectively. Whereas, compound [(O3PCH2PO3)4W12O36]16− was a potent and selective inhibitor of butyrylcholinesterase with IC50 value of 0.18 ± 0.05 μM. In general, POMs were found to be effective cholinesterase inhibitors in terms of efficiency as well as selectivity and represent non-classical cholinesterase inhibitors.
KeywordsAcetylcholinesterase Anti-Alzheimer Butyrylcholinesterase Enzyme Inhibition Polyoxometalates
This work was financially supported by COMSTECH–TWAS and German-Pakistani Research Collaboration Program.
- Alptuzun V, Prinz M, Horr V, Scheiber J, Radacki K, Fallarero A, Vuorela P, Engels B, Braunschweig H, Erciyas E, Holzgrabe U (2010) Interaction of (benzylidene-hydrazono)-1,4-dihydropyridines with beta-amyloid, acetylcholine, and butyrylcholine esterases. Bioorg Med Chem 18:2049–2059PubMedCrossRefGoogle Scholar
- Contant R, Klemperer WG, Yaghi O (2007) Potassium Octadecatungstodiphosphates(V) and Related Lacunary Compounds. In: Inorganic Syntheses, pp 104-111: John Wiley & Sons, IncGoogle Scholar
- Inoue M, Suzuki T, Fujita Y, Oda M, Matsumoto N, Iijima J, Yamase T (2006a) Synergistic effect of polyoxometalates in combination with oxacillin against methicillin-resistant and vancomycin-resistant Staphylococcus aureus: a high initial inoculum of 1 x 108 cfu/ml for in vivo test. Biomed Pharmacother 60:220–226PubMedCrossRefGoogle Scholar
- Inoue M, Suzuki T, Fujita Y, Oda M, Matsumoto N, Yamase T (2006b) Enhancement of antibacterial activity of beta-lactam antibiotics by [P2W18O62]6-, [SiMo12O40]4-, and [PTi2W10O40]7- against methicillin-resistant and vancomycin-resistant Staphylococcus aureus. J Inorg Biochem 100:1225–1233PubMedCrossRefGoogle Scholar
- Komloova M, Musilek K, Horova A, Holas O, Dohnal V, Gunn-Moore F, Kuca K (2011) Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors–implications for early myasthenia gravis treatment. Bioorg Med Chem Lett 21:2505–2509PubMedCrossRefGoogle Scholar
- Korabecny J, Musilek K, Holas O, Binder J, Zemek F, Marek J, Pohanka M, Opletalova V, Dohnal V, Kuca K (2010) Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease. Bioorg Med Chem Lett 20:6093–6095PubMedCrossRefGoogle Scholar
- Marco JL, de los Rios C, Garcia AG, Villarroya M, Carreiras MC, Martins C, Eleuterio A, Morreale A, Orozco M, Luque FJ (2004) Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2 + channels and nicotinic receptors. Bioorg Med Chem 12:2199–2218PubMedCrossRefGoogle Scholar
- Samadi A, Chioua M, Bolea I, de los Ríos C, Iriepa I, Moraleda I, Bastida A, Esteban G, Unzeta M, Gálvez E, Marco-Contelles J (2011) Synthesis, biological assessment and molecular modeling of new multipotent MAO and cholinesterase inhibitors as potential drugs for the treatment of Alzheimer’s disease. Eur J Med Chem 46:4665–4668PubMedCrossRefGoogle Scholar
- Tasso B, Catto M, Nicolotti O, Novelli F, Tonelli M, Giangreco I, Pisani L, Sparatore A, Boido V, Carotti A, Sparatore F (2011) Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyl- and butyrylcholinesterase with potential in Alzheimer’s disease. Eur J Med Chem 46:2170–2184PubMedCrossRefGoogle Scholar