氨基磺酸盐及其治疗潜力。
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韦娜姆，斯科扎法瓦A，蒙特罗JL，苏普兰
氨基磺酸盐及其治疗潜力。
医学研究，2005年3月25日(2):186-228。
- PubMed ID
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15478125 (PubMed视图]
- 摘要
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从非常简单的氨基磺酸分子出发，可以得到o -取代、n -取代或二/三取代的氨基磺酸酯，它们表现出特定的生物活性，已或已开始被用于多种治疗药物的设计。其中氨基酰基- trna合成酶(aaRSs)的磺胺类抑制剂(sulfamate inhibitors of amino酰基- trna synthetases, aaRSs)是最近报道的一类全新抗生素，可用于对抗耐药感染。还获得了包含氨基磺酸酯部分的抗病毒药物，研究了至少两种此类衍生物:核苷/核苷酸人类免疫缺陷病毒(HIV)逆转录酶抑制剂和HIV蛋白酶抑制剂(pi)。在日益增多的抗癌药物中，氨基磺酸盐占据着特殊的地位，迄今为止至少有两个重要的靶点被证实:甾体硫酸酯酶(STSs)和碳酸酐酶(CAs)。在过去几年中，磺胺类STSs抑制剂的数量令人印象深刻，其中一些化合物，如667COUMATE，正在进行治疗激素依赖性肿瘤(乳腺癌和前列腺癌)的临床试验。这一领域正在迅速发展，许多类型的新抑制剂不断被报道和设计，以增加它们的抗肿瘤特性，并减少不需要的特性(例如，雌激素，第一代此类抑制剂遇到的问题，如EMATE)。在CA的众多同工酶中，至少有两种CA IX和CA XII在肿瘤中高度过表达，而在正常组织中普遍不存在。抑制肿瘤相关的ca被假设为导致治疗癌症的新治疗方法。许多氨基磺酸酯是非常有效的(低纳摩尔)CA抑制剂。最近报道了研究得最好的同工酶CA II与三种磺胺酸(氨基磺酸、托吡酯和EMATE)的x射线晶体结构，这为新抑制剂的基本原理药物设计提供了依据。 Indeed, low nanomolar CA IX inhibitors of the sulfamate type have been reported, although such compounds also act as efficient inhibitors of isozymes CA I and II, which are not associated with tumors. A large number of anti-convulsant sulfamates have been described, with one such compound, topiramate, being widely used clinically as anti-epileptic drug. By taking into consideration a side effect of topiramate, an anti-epileptic drug leading to weight loss in some patients, it has recently been proposed to use this drug and related sulfamates for the treatment of obesity. The rationale of this use is based on the inhibition of the mitochondrial CA isozyme, CA V, involved in lipogenesis. Some sulfamates were also shown to possess potent inhibitory activity against acyl coenzyme A:cholesterol acyltransferase, an enzyme involved in cholesterol metabolism. One such agent, avasimibe, is in advanced clinical trials for the treatment of hyperlipidemia and atherosclerosis. Thus, the sulfamate moiety offers very attractive possibilities for the drug design of various pharmacological agents, which are on one hand due to the relative ease with which such compounds are synthesized, and on the other one, due to the fact that biological activity of most of them is impressive.