Synthesis and in vitro evaluation of pteridine analogues as monoamine oxidase B and nitric oxide synthase inhibitors |
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Authors: | Louis HA Prins Jacobus P Petzer Sarel F Malan |
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Institution: | aPharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa |
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Abstract: | Monoamine oxidase B (MAO-B) and nitric oxide synthase (NOS) have both been implicated in the pathology of neurodegenerative diseases. In an attempt to design dual-target-directed drugs that inhibit both these enzymes, a series of pteridine-2,4-dione analogues were synthesised. The compounds were found to be relatively weak NOS inhibitors but showed promising MAO-B activity with 6-amino-5-(E)-3-(3-chloro-phenyl)-prop-2-en-(E)-ylideneamino]-1,3-dimethyl-1H-pyrimidine-2,4-dione and 6-(E)-2-(3-chloro-phenyl)-vinyl]-1,3-dimethyl-1H-pteridine-2,4-dione inhibiting MAO-B with IC50 values of 0.602 and 0.314 μM, respectively. The pteridine-2,4-dione analogues thus show promise as scaffolds for the development of potent reversible MAO-B inhibitors and as observed in earlier studies, the most potent inhibitors were obtained with 3-chlorostyryl substitution. |
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Keywords: | Monoamine oxidase B Nitric oxide synthase Pteridine-2 4-dione Dual-target-directed ligands |
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