Rubino Maria Teresa, Agamennone Mariangela, Campestre Cristina, Fracchiolla Giuseppe, Laghezza Antonio, Loiodice Fulvio, Nuti Elisa, Rossello Armando, Tortorella Paolo
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via Orabona 4, 70126 Bari, Italy.
ChemMedChem. 2009 Mar;4(3):352-62. doi: 10.1002/cmdc.200800324.
Eleven simple alpha-sulfonylphosphonates, new analogues of previously reported alpha-sulfonylaminophosphonates, were prepared and tested as MMP inhibitors. The IC(50) values of most of these compounds are in the nanomolar range against MMP-2, -8, -13, and -14. Compound 11 proved to be the most effective inhibitor of MMP-2 (IC(50) = 60 nM), with interesting selectivity versus the antitarget enzymes MMP-3 and MMP-9. The mode of binding of the new phosphonates in the active site of MMP-2 was studied, and variations in inhibition was explained by means of molecular modeling.
制备了11种简单的α-磺酰基膦酸酯，它们是先前报道的α-磺酰基氨基膦酸酯的新类似物，并作为基质金属蛋白酶（MMP）抑制剂进行了测试。这些化合物中的大多数对MMP-2、-8、-13和-14的半数抑制浓度（IC50）值处于纳摩尔范围。化合物11被证明是MMP-2最有效的抑制剂（IC50 = 60 nM），对非靶标酶MMP-3和MMP-9具有有趣的选择性。研究了新膦酸酯在MMP-2活性位点的结合模式，并通过分子模拟解释了抑制作用的差异。
