Department of Biology, University Roma Tre, Rome, Italy.
J Enzyme Inhib Med Chem. 2013 Jun;28(3):463-7. doi: 10.3109/14756366.2011.650691. Epub 2012 Feb 3.
Acetylpolyamine and spermine oxidases are involved in the catabolism of polyamines. The discovery of selective inhibitors of these enzymes represents an important tool for the development of novel anti-neoplastic drugs. Here, a comparative study on acetylpolyamine and spermine oxidases inhibition by the polyamine analogue chlorhexidine is reported. Chlorhexidine is an antiseptic diamide, commonly used as a bactericidal and bacteriostatic agent. Docking simulations indicate that chlorhexidine binding to these enzymes is compatible with the stereochemical properties of both acetylpolyamine oxidase and spermine oxidase active sites. In fact, chlorhexidine is predicted to establish several polar and hydrophobic interactions with the active site residues of both enzymes, with binding energy values ranging from -7.6 to -10.6 kcal/mol. In agreement with this hypothesis, inhibition studies indicate that chlorhexidine behaves as a strong competitive inhibitor of both enzymes, values of Ki being 0.10 μM and 0.55 μM for acetylpolyamine oxidase and spermine oxidase, respectively.
乙酰多胺和精脒氧化酶参与多胺的分解代谢。这些酶的选择性抑制剂的发现为新型抗肿瘤药物的开发提供了重要工具。本文报道了多胺类似物氯己定对乙酰多胺氧化酶和精脒氧化酶抑制作用的比较研究。氯己定是一种抗菌双酰胺，通常用作杀菌和抑菌剂。对接模拟表明，氯己定与这些酶的结合符合乙酰多胺氧化酶和精脒氧化酶活性位点的立体化学性质。事实上，氯己定预计与两种酶的活性位点残基建立多个极性和疏水性相互作用，结合能值范围为-7.6 至-10.6 kcal/mol。与该假说一致，抑制研究表明氯己定是两种酶的强竞争性抑制剂，Ki 值分别为 0.10 μM 和 0.55 μM。
