Maczyński Marcin, Ryng Stanisław, Artym Jolanta, Kocieba Maja, Zimecki Michał, Brudnik Katarzyna, Jodkowski Jerzy T
Acta Pol Pharm. 2014 Jan-Feb;71(1):71-83.
Potential immunological activities of three compounds: RM54 and its two derivatives RM55 and RM56, were evaluated in several, selected in vitro and in vivo tests such as: mitogen-induced lymphocyte proliferation, cytokine production, the humoral immune response in vitro and carrageenan test. Leflunomide served as a reference drug. The studied compounds showed differential, generally immunosuppressive properties. RM56 exhibited stronger suppressive activities as compared to RM54 and RM55. In particular, RM56 displayed the strongest activity in suppression of the carrageenan inflammation that was correlated with strong suppression of the humoral immune response in vitro and lymphocyte proliferation. Density Functional Theory (DFT) was employed to shed a light on molecular properties of the investigated compounds. The geometrical parameters of the studied molecular structures were fully optimized at the B3LYP/6-311G(d,p) level. The atomic charges distribution derived on the base of the Mulliken population analysis was correlated with immunological activity of RM54, RM55 and RM56. The obtained relationships show that the isoxazole ring plays an important role in the observed immunological activities. We also suggest that due to strong anti-inflammatory and anti-proliferative properties of RM-56, potential therapeutic applications of this derivative can be broad.
对三种化合物RM54及其两种衍生物RM55和RM56的潜在免疫活性进行了多项体外和体内试验评估，如丝裂原诱导的淋巴细胞增殖、细胞因子产生、体外体液免疫反应和角叉菜胶试验。来氟米特作为参考药物。所研究的化合物表现出不同的、一般为免疫抑制的特性。与RM54和RM55相比，RM56表现出更强的抑制活性。特别是，RM56在抑制角叉菜胶炎症方面表现出最强的活性，这与体外体液免疫反应和淋巴细胞增殖的强烈抑制相关。采用密度泛函理论（DFT）来阐明所研究化合物的分子性质。在B3LYP/6-311G(d,p)水平上对所研究分子结构的几何参数进行了完全优化。基于Mulliken布居分析得出的原子电荷分布与RM54、RM55和RM56的免疫活性相关。所得到的关系表明异恶唑环在观察到的免疫活性中起重要作用。我们还认为，由于RM-56具有强大的抗炎和抗增殖特性，该衍生物的潜在治疗应用可能很广泛。
