Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA, Buenos Aires, Argentina.
CONICET-Universidad de Buenos Aires, Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), C1428EHA, Buenos Aires, Argentina.
ChemMedChem. 2024 Sep 2;19(17):e202400063. doi: 10.1002/cmdc.202400063. Epub 2024 Jul 12.
The chemical and biological interest in this element and the molecules bearing selenium has been exponentially growing over the years. Selenium, formerly designated as a toxin, becomes a vital trace element for life that appears as selenocysteine and its dimeric form, selenocystine, in the active sites of selenoproteins, which catalyze a wide variety of reactions, including the detoxification of reactive oxygen species and modulation of redox activities. From the point of view of drug developments, organoselenium drugs are isosteres of sulfur-containing and oxygen-containing drugs with the advantage that the presence of the selenium atom confers antioxidant properties and high lipophilicity, which would increase cell membrane permeation leading to better oral bioavailability. This statement is the paramount relevance considering the big number of clinically employed compounds bearing sulfur or oxygen atoms in their structures including nucleosides and carbohydrates. Thus, in this article we have focused on the relevant features of the application of selenium in medicinal chemistry. With the increasing interest in selenium chemistry, we have attempted to highlight the most significant published data on this subject, mainly concentrating the analysis on the last years. In consequence, the recent advances of relevant pharmacological organoselenium compounds are discussed.
近年来,人们对该元素及其含硒分子的化学和生物学兴趣呈指数级增长。硒曾经被认为是一种毒素,现在已成为生命必需的微量元素,以硒代半胱氨酸及其二聚体形式(硒代胱氨酸)存在于硒蛋白的活性部位,催化各种反应,包括活性氧物质的解毒和氧化还原活性的调节。从药物开发的角度来看,有机硒药物是含硫和含氧药物的等排体,其优势在于硒原子的存在赋予了抗氧化性质和高亲脂性,这将增加细胞膜渗透,从而提高口服生物利用度。考虑到大量临床应用的化合物在其结构中含有硫或氧原子,包括核苷和碳水化合物,这一说法至关重要。因此,本文重点关注了硒在药物化学中的应用的相关特征。随着对硒化学兴趣的增加,我们试图突出该主题最有意义的已发表数据,主要集中在近几年的分析上。因此,讨论了相关药理学有机硒化合物的最新进展。