Hron Rebecca J, Jursic Branko S, Neumann Donna M
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, United States.
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, United States; STEPHARM, LLC., PO Box 24220, New Orleans, LA 70184, United States.
Bioorg Med Chem. 2016 Dec 1;24(23):6183-6193. doi: 10.1016/j.bmc.2016.09.074. Epub 2016 Oct 4.
Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (ClogP), acidic strength (calculated pK), and polar surface area (PSA) were used to design a diverse structural library of these compounds. From six different structural motifs and 136 compounds, a handful of examples with moderate (100μg/ml), good (10μg/ml) and excellent (1μg/ml) glioblastoma activity were elucidated.
基于美巴龙的初始（先导）结构设计、制备了六种结构基序，并针对胶质母细胞瘤LN-229细胞系进行了测试。为了寻找最佳的胶质母细胞瘤活性，对三个不同的结构部分进行了修饰：1,3-二氮杂环己烷部分、芳基部分和杂原子连接基。诸如亲脂性（ClogP）、酸性强度（计算得到的pK）和极性表面积（PSA）等计算得到的分子描述符被用于设计这些化合物的多样化结构库。从六种不同的结构基序和136种化合物中，阐明了一些具有中度（100μg/ml）、良好（10μg/ml）和优异（1μg/ml）胶质母细胞瘤活性的实例。
