Ghosh Payel, Thanadath Megha, Bagchi Manish C
Drug Design, Development and Molecular Modelling Division, Indian Institute of Chemical Biology, Jadavpur, Calcutta, India.
Mol Divers. 2006 Aug;10(3):415-27. doi: 10.1007/s11030-006-9018-4. Epub 2006 Aug 2.
The re-emergence of tuberculosis infections, which are resistant to conventional drug therapy, has steadily risen in the last decade and as a result of that, fluoroquinolone drugs are being used as the second line of action. But there is hardly any study to examine specific structure activity relationships of quinolone antibacterials against mycobacteria. In this paper, an attempt has been made to establish a quantitative structure activity relationship modeling for a series of quinolone compounds against Mycobacterium fortuitum and Mycobacterium smegmatis. Due to lack of sufficient physicochemical data for the anti-mycobacterial compounds, it becomes very difficult to develop predictive methods based on experimental data. The present paper is an effort for the development of QSARs from the standpoint of physicochemical, constitutional, geometrical, electrostatic and topological indices. Molecular descriptors have been calculated solely from the chemical structure of N-1, C-7 and 8 substituted quinolone compounds and ridge regression models have been developed which can explain a better structure-activity relationship. Consideration of an intermolecular similarity analysis approach that led to a successful computer program development in PERL language has been used for comparing the influence of various molecular descriptors in different data subsets. The comparison of relative effectiveness of the calculated descriptors in our ridge regression model gives rise to some interesting results.
在过去十年中,对传统药物治疗具有抗性的结核感染再度出现且呈稳步上升趋势,因此氟喹诺酮类药物正被用作二线治疗药物。但是,几乎没有任何研究来考察喹诺酮类抗菌药物针对分枝杆菌的具体构效关系。在本文中,已尝试针对一系列喹诺酮化合物建立针对偶然分枝杆菌和耻垢分枝杆菌的定量构效关系模型。由于抗分枝杆菌化合物缺乏足够的物理化学数据,基于实验数据开发预测方法变得非常困难。本文从物理化学、结构、几何、静电和拓扑指数的角度致力于开发定量构效关系。分子描述符仅根据N-1、C-7和8取代喹诺酮化合物的化学结构计算得出,并且已开发出能解释更好构效关系的岭回归模型。考虑了一种分子间相似性分析方法,该方法导致了用PERL语言成功开发计算机程序,已用于比较不同数据子集中各种分子描述符的影响。我们的岭回归模型中计算出的描述符相对有效性的比较产生了一些有趣的结果。