ABSTRACT Alzheimer’s disease is one of the leading causes of disability and death in the global scenario. Acetylcholinesterase inhibitors are symptomatically involved in the therapeutic management of Alzheimer’s disease. Due to the prophetic capability of SMILES-based QSAR studies, the current method explored its efficiency for designing novel inhibitors of acetylcholinesterase enzyme. Two newly introduced validation parameters (the ideality of correlation (IIC) and the correlation contradiction index (CCI)) were studied for further validating the predictive capability of developed models. The index of ideality of correlation was found to have a positive effect on models developed in comparison to models developed without IIC. The structural features accountable for intensifying the inhibitory activity were identified by performing QSAR modelling studies on 60 acetylcholinesterase inhibitors from the literature. Based on the molecular features identified designing of new molecules was accomplished and was found to have satisfactory inhibitory potential. Docking interactions of designed molecules pointed the importance of position of nitro group, aromatic ring and alkyl substitution in influencing the inhibitory activity and binding interactions. The designed compound DD2 was found to have highest inhibitory potential (4.33) and binding affinity (−11.2 kcal mol−1).

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相关性理想指数和相关矛盾指数：对乙酰胆碱酯酶抑制剂的综合研究

摘要 阿尔茨海默病是全球范围内导致残疾和死亡的主要原因之一。乙酰胆碱酯酶抑制剂在症状上参与阿尔茨海默病的治疗管理。由于基于 SMILES 的 QSAR 研究的预测能力，目前的方法探索了其设计新型乙酰胆碱酯酶抑制剂的效率。研究了两个新引入的验证参数（相关理想性 (IIC) 和相关矛盾指数 (CCI)），以进一步验证开发模型的预测能力。与没有 IIC 开发的模型相比，相关性理想指数对开发的模型具有积极影响。通过对文献中的 60 种乙酰胆碱酯酶抑制剂进行 QSAR 建模研究，确定了增强抑制活性的结构特征。基于已识别的分子特征，设计了新分子并发现其具有令人满意的抑制潜力。设计分子的对接相互作用表明硝基、芳环和烷基取代的位置在影响抑制活性和结合相互作用中的重要性。发现设计的化合物 DD2 具有最高的抑制潜力 (4.33) 和结合亲和力 (-11.2 kcal mol-1)。设计分子的对接相互作用表明硝基、芳环和烷基取代的位置在影响抑制活性和结合相互作用中的重要性。发现设计的化合物 DD2 具有最高的抑制潜力 (4.33) 和结合亲和力 (-11.2 kcal mol-1)。设计分子的对接相互作用表明硝基、芳环和烷基取代的位置在影响抑制活性和结合相互作用中的重要性。发现设计的化合物 DD2 具有最高的抑制潜力 (4.33) 和结合亲和力 (-11.2 kcal mol-1)。