Department of Chemistry, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran.
J Enzyme Inhib Med Chem. 2010 Dec;25(6):827-35. doi: 10.3109/14756361003691860. Epub 2010 Mar 30.
Some new α-aminomethylenephosphonic acids 1-11 were synthesised and characterised by (1)H, (13)C, (31)P NMR, IR spectroscopy and elemental analysis. The potencies of these compounds to inhibit human erythrocyte acetylcholinesterase (hAChE, EC 3.1.1.7) were studied by a modified Ellman's method. In addition, the log P values were computed by Hyperchem software. Here, alendronate was used as a reference inhibitor. Results showed that the IC(50) values ranged from 9.11 to 28.72 mM. The half maximal inhibitory concentration (IC(50)) value decreased with an increasing number of carbon atoms of the amine group in compounds 1-5. Also, in most cases, increasing the number of carbon atoms led to enhancement of the toxicity as predicted by the log P values. Using Lineweaver-Burk and Dixon analysis, it was indicated that compounds 1-10 are mixed inhibitors while compound 11 is a coupling or uncompetitive inhibitor. The results showed that the electronic changes have ignorable effects, steric influence is important in some cases, but the lipophilicity parameter is the most significant factor in hAChE inhibition by bisphosphonates.
一些新的α-氨甲基膦酸化合物 1-11 通过（1）H、（13）C、（31）P NMR、IR 光谱和元素分析进行了合成和表征。通过改良的 Ellman 法研究了这些化合物抑制人红细胞乙酰胆碱酯酶（hAChE，EC 3.1.1.7）的效力。此外，通过 Hyperchem 软件计算了 log P 值。在这里，阿仑膦酸钠被用作参考抑制剂。结果表明，IC（50）值范围为 9.11 至 28.72 mM。化合物 1-5 中胺基团的碳原子数增加，IC（50）值降低。同样，在大多数情况下，根据 log P 值预测，碳原子数的增加会导致毒性增强。通过 Lineweaver-Burk 和 Dixon 分析表明，化合物 1-10 是混合抑制剂，而化合物 11 是偶联或非竞争性抑制剂。结果表明，电子变化的影响可以忽略不计，在某些情况下空间位阻很重要，但亲脂性参数是双膦酸盐抑制 hAChE 的最主要因素。
