Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory, Faculty of Pharmacy, Medical University of Lublin, 4 A Chodzki St., 20-093 Lublin, Poland.
Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, 1 Pigonia St., 35-310 Rzeszow, Poland.
Molecules. 2022 Mar 30;27(7):2239. doi: 10.3390/molecules27072239.
Neurodegenerative and mental diseases are serious medical, economic and social problems. Neurodegeneration is referred to as a pathological condition associated with damage to nerve cells leading to their death. Treatment of neurodegenerative diseases is at present symptomatic only, and novel drugs are urgently needed which would be able to stop disease progression. We performed screening of reactive oxygen species, reactive nitrogen species, glutathione and level intracellular Ca. The studies were assessed using one-way ANOVA of variance with Dunnett's post hoc test. Previously, we reported D2AAK1 as a promising compound for the treatment of neurodegenerative and mental disorders. Here, we show a screening of D2AAK1 derivatives aimed at the selection of the compound with the most favorable pharmacological profile. Selected compounds cause an increase in the proliferation of a hippocampal neuron-like cell line, changes in the levels of reactive oxygen and nitrogen forms, reduced glutathione and a reduced intracellular calcium pool. Upon analyzing the structure-activity relationship, we selected the compound with the most favorable profile for a neuroprotective activity for potential application in the treatment of neurodegenerative diseases.
神经退行性和精神疾病是严重的医学、经济和社会问题。神经退行性变是指与神经细胞损伤相关的病理状态，导致其死亡。目前，神经退行性疾病的治疗仅对症治疗，急需能够阻止疾病进展的新药。我们进行了活性氧、活性氮、谷胱甘肽和细胞内 Ca 水平的筛选。使用单因素方差分析和 Dunnett 事后检验评估研究。以前，我们报道了 D2AAK1 是治疗神经退行性和精神障碍的有前途的化合物。在这里，我们展示了 D2AAK1 衍生物的筛选，旨在选择具有最有利的药理特性的化合物。选定的化合物可增加海马神经元样细胞系的增殖，改变活性氧和氮形式、还原型谷胱甘肽和细胞内钙库的水平。在分析结构-活性关系时，我们选择了具有最有利的神经保护活性的化合物，用于治疗神经退行性疾病的潜在应用。
