Provensi Gustavo, Costa Alessia, Rani Barbara, Becagli Maria Vittoria, Vaiano Fabio, Passani Maria Beatrice, Tanini Damiano, Capperucci Antonella, Carradori Simone, Petzer Jacobus P, Petzer Anél, Vullo Daniela, Costantino Gabriele, Blandina Patrizio, Angeli Andrea, Supuran Claudiu T
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.
Department of Health Sciences, University of Florence, Viale Pieraccini 6 Florence, Florence, Italy.
Eur J Med Chem. 2022 Dec 15;244:114828. doi: 10.1016/j.ejmech.2022.114828. Epub 2022 Oct 7.
Cognitive deficits are enduring and disabling symptoms for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. In this study, we reported the synthesis of β-arylchalcogeno amines bearing sulfurated, selenated, and tellurated moieties (2-4) which are structurally related to amphetamine with good activation properties for Carbonic Anhydrases (CAs) isoforms present in the cortical and hippocampal brain structures (hCA IV and hCA XIV). In addition, these compounds showed selective inhibition against the Monoamine oxidase (MAO) A isoform. In vivo evaluation of two derivatives (2a and 3a) revealed procognitive effects in the object recognition and social discrimination tests. Interestingly, these compounds, despite having a similar structure to amphetamine, did not caused hypophagia or hyperlocomotion, two effects often observed following the administration of amphetamine-like drugs. In this context, β-arylchalcogeno amines may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases such as attention deficit disorder, Parkinson's disease-related cognitive dysfunction and cognitive disorders associated with depression.
认知缺陷是许多重症精神疾病患者长期存在且导致功能障碍的症状，而目前的药物对这些损害的治疗效果不佳。在本研究中，我们报道了含有硫化、硒化和碲化部分的β-芳基硫属元素胺（2-4）的合成，这些化合物在结构上与苯丙胺相关，对存在于大脑皮质和海马结构中的碳酸酐酶（CAs）同工型（hCA IV和hCA XIV）具有良好的激活特性。此外，这些化合物对单胺氧化酶（MAO）A同工型表现出选择性抑制作用。对两种衍生物（2a和3a）的体内评估显示，它们在物体识别和社会辨别测试中具有促认知作用。有趣的是，尽管这些化合物的结构与苯丙胺相似，但它们并未引起食欲减退或运动亢进，而这两种效应在服用苯丙胺类药物后经常会出现。在这种情况下，β-芳基硫属元素胺可能有助于改善与神经退行性疾病和精神疾病相关的认知衰退症状，如注意力缺陷障碍、帕金森病相关的认知功能障碍以及与抑郁症相关的认知障碍。
