Department of Chemistry, Saurashtra University, Rajkot, 360005, India.
Chem Biol Drug Des. 2013 Dec;82(6):669-84. doi: 10.1111/cbdd.12178.
Frequency of tuberculosis is progressively increasing worldwide. New emerging strains of bacilli that are emerging are resistant to the currently available drugs which make this issue more alarming. In this regard, a series of substituted quinolinyl chalcones, quinolinyl pyrimidines, and pyridines were synthesized and evaluated for their antitubercular activity in vitro against Mycobacterium tuberculosis H37 RV. To establish the role of the 2-chloroquinoline nucleus as a pharmacophoric group and study its influence on the antimycobacterial activity, a 3D-QSAR study based on CoMFA and CoMSIA was undertaken on this set of 2-chloroquinoline derivatives. Statistically significant models that are able to well correlate the antimycobacterial activity with the chemical structures of the 2-chloroquinolines have been developed. The contour maps resulting from the best CoMFA and CoMSIA models were used to identify the structural features relevant to the biological activity in this series of analogs. Further analysis of these interaction-field contour maps also showed a high level of internal consistency. The information obtained from the field 3-D contour maps may be fruitfully utilized in the design of more potent 2-chloroquinoline-based analogs as potential antitubercular candidates.
结核病的发病率在全球范围内呈逐渐上升趋势。新出现的分枝杆菌菌株对现有药物具有耐药性，这使得问题更加严重。在这方面，我们合成了一系列取代的喹啉查耳酮、喹啉嘧啶和吡啶，并评估了它们对结核分枝杆菌 H37 RV 的体外抗结核活性。为了确定 2-氯喹啉核作为药效团的作用，并研究其对抗分枝杆菌活性的影响，我们对这组 2-氯喹啉衍生物进行了基于 CoMFA 和 CoMSIA 的 3D-QSAR 研究。已经开发出能够很好地将抗分枝杆菌活性与 2-氯喹啉化学结构相关联的统计学上显著模型。从最佳 CoMFA 和 CoMSIA 模型得出的等高线图用于确定该系列类似物中与生物活性相关的结构特征。对这些相互作用场等高线图的进一步分析也显示出高度的内部一致性。从场 3-D 等高线图获得的信息可有效地用于设计更有效的基于 2-氯喹啉的类似物，作为潜在的抗结核候选物。
