A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were foun...A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were found to be selective towards h MAO-B, while two were non-selective（6 and 20） and one（18）selective towards h MAO-A. Compound 17（Ki = 0.10 0.01 mmol/L） was found to be equally potent and selective towards h MAO-B, when compared with the standard drug Selegiline（Ki = 0.12 0.01 mmol/L）.Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences h MAO-B inhibitory potency, while their structural bulkiness influences selectivity between h MAO-A and h MAO-B.Molecular docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity.展开更多
基金Birla Institute of Technology for providing financial support as a prestigious Institute fellowship
文摘A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were found to be selective towards h MAO-B, while two were non-selective（6 and 20） and one（18）selective towards h MAO-A. Compound 17（Ki = 0.10 0.01 mmol/L） was found to be equally potent and selective towards h MAO-B, when compared with the standard drug Selegiline（Ki = 0.12 0.01 mmol/L）.Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences h MAO-B inhibitory potency, while their structural bulkiness influences selectivity between h MAO-A and h MAO-B.Molecular docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity.
