Dolezal R, Van Damme S, Bultinck P, Waisser K
Department of Inorganic and Organic chemistry, Charles University, Heyrovského 1203, Hradec Králové 50003, Czech Republic.
Eur J Med Chem. 2009 Feb;44(2):869-76. doi: 10.1016/j.ejmech.2008.04.020. Epub 2008 May 6.
Quantitative relationships between the molecular structure and the biological activity of 49 isosteric salicylamide derivatives as potential antituberculotics with a new mechanism of action against three Mycobacterial strains were investigated. The molecular structures were represented by quantum chemical B3LYP/6-31G( *) based molecular descriptors. A resulting set of 220 molecular descriptors, including especially electronic properties, was statistically analyzed using multiple linear regression, resulting in acceptable and robust QSAR models. The best QSAR model was found for Mycobacterium tuberculosis (r(2)=0.92; q(2)=0.89), and somewhat less good QSAR models were found for Mycobacterium avium (r(2)=0.84; q(2)=0.78) and Mycobacterium kansasii (r(2)=0.80; q(2)=0.56). All QSAR models were cross-validated using the leave-10-out procedure.
研究了49种等排水杨酸酰胺衍生物的分子结构与生物活性之间的定量关系，这些衍生物作为潜在的抗结核药物，对三种分枝杆菌菌株具有新的作用机制。分子结构由基于量子化学B3LYP/6-31G(*)的分子描述符表示。使用多元线性回归对包括特别是电子性质在内的220个分子描述符的结果集进行统计分析，得到了可接受且稳健的QSAR模型。发现针对结核分枝杆菌的最佳QSAR模型（r(2)=0.92；q(2)=0.89），而针对鸟分枝杆菌（r(2)=0.84；q(2)=0.78）和堪萨斯分枝杆菌（r(2)=0.80；q(2)=0.56）的QSAR模型稍差。所有QSAR模型均使用留一法进行交叉验证。
