Debnath Bikash, Gayen Shovanlal, Basu Anindya, Ghosh Balaram, Srikanth Kolluru, Jha Tarun
Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, PO Box No 17020, Jadavpur University, Kolkata 700 032, India.
Bioorg Med Chem. 2004 Dec 1;12(23):6137-45. doi: 10.1016/j.bmc.2004.09.003.
Importance of atom-level topological descriptors like electrotopological state atom (E-state) index in QSAR study is increasing. These descriptors help to relate structure and activity at atomic/fragmental level. In view of the earlier success of E-state index on some azidopyridinyl neonicotinoid insecticides, a relatively new atom-level topological descriptor; refractotopological state atom (R-state) index was used in this work. This was used to identify the important atoms/fragments related to dispersive/van der Waals interactions of neonicotinoids with the nicotinic acetylcholine receptor (nAChR). This study showed the structural requirements for the mammal alpha(4)beta(2) and Drosophila nAChR agonistic activity. It also revealed that substituted imine, nitromethylene at X-position were selective to the insecticidal activity. Azido substitution at pyridine ring of neonicotinoids disfavored the binding with the receptors. This study confirmed the validity of the R-state index as a new tool for quantitative structure-activity relationships. It has the ability to find out the required structural features as well as to predict the activity of the neonicotinoids.
像电子拓扑状态原子（E-态）指数这样的原子水平拓扑描述符在定量构效关系（QSAR）研究中的重要性日益增加。这些描述符有助于在原子/片段水平上关联结构与活性。鉴于E-态指数在某些叠氮吡啶基新烟碱类杀虫剂上取得的早期成功，本研究使用了一种相对较新的原子水平拓扑描述符——折射拓扑状态原子（R-态）指数。该指数用于识别与新烟碱类与烟碱型乙酰胆碱受体（nAChR）的色散/范德华相互作用相关的重要原子/片段。本研究表明了对哺乳动物α(4)β(2)和果蝇nAChR激动活性的结构要求。研究还揭示，X位的取代亚胺、硝基亚甲基对杀虫活性具有选择性。新烟碱类吡啶环上的叠氮取代不利于与受体的结合。本研究证实了R-态指数作为定量构效关系新工具的有效性。它有能力找出所需的结构特征，并预测新烟碱类的活性。
