This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR...This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR) method. The molecules were optimized at the level DFT/B3LYP/6-31 + G (d, p), to obtain the molecular descriptors. We used three statistical learning tools namely, the linear multiple regression (LMR) method, the nonlinear regression (NLMR) and the artificial neural network (ANN) method. These methods allowed us to obtain three (3) quantitative models from the quantum descriptors that are, chemical potential (μ), polarizability (α), bond length l (C = N), and lipophilicity. These models showed good statistical performance. Among these, the ANN has a significantly better predictive ability R<sup>2</sup> = 0.9995;RMSE = 0.0149;F = 31879.0548. The external validation tests verify all the criteria of Tropsha et al. and Roy et al. Also, the internal validation tests show that the model has a very satisfactory internal predictive character and can be considered as robust. Moreover, the applicability range of this model determined from the levers shows that a prediction of the pMIC of the new benzimidazole derivatives is acceptable when its lever value is lower than 1.展开更多
目的建立H37Rv结核分支杆菌诱导的兔脊柱结核模型。方法选择未致敏处理的新西兰大白兔48只,在第5腰椎近椎间盘处钻孔,并填充明胶海绵,注射0.5 mg/0.1 m L结核菌悬液,术后观察新西兰大白兔一般情况,并用影像学、组织病理学、细菌学等检...目的建立H37Rv结核分支杆菌诱导的兔脊柱结核模型。方法选择未致敏处理的新西兰大白兔48只,在第5腰椎近椎间盘处钻孔,并填充明胶海绵,注射0.5 mg/0.1 m L结核菌悬液,术后观察新西兰大白兔一般情况,并用影像学、组织病理学、细菌学等检查对兔脊柱结核模型进行评估。结果受H37Rv结核菌株感染后的新西兰大白兔,局部反应较明显,全身反应较轻。48只兔中38只兔完成实验,10只因死亡、术后截瘫被淘汰,15只兔分别于术后第5、6周出现进食欠佳、消瘦,但生命体征平稳,其中4只术区局部肿胀,6只出现下肢运动障碍;其余23只兔术后进食较好,体质量未见明显变化。术后3个月行外科手术,暴露致病兔椎体,38只兔中29只兔椎体可见虫噬样改变,9只兔椎体未见明显变化。术中取脓肿形成的兔脓液培养示结核分枝杆菌生长;取周围软组织、脓壁行苏木精-伊红色(HE)染色,示坏死灶形成、较多炎细胞聚集、淋巴细胞、较少上皮样细胞,骨结构紊乱或消失。建立模型成功率为76.3%(29/38)。结论使用0.5 mg/0.1 m L的H37Rv标准菌株感染的新西兰白兔结核模型建立成功。展开更多
文摘This work was carried out on a series of twenty-two (22) benzimidazole derivatives with inhibitory activities against Mycobacterium tuberculosis H37Rv by applying the Quantitative Structure-Activity Relationship (QSAR) method. The molecules were optimized at the level DFT/B3LYP/6-31 + G (d, p), to obtain the molecular descriptors. We used three statistical learning tools namely, the linear multiple regression (LMR) method, the nonlinear regression (NLMR) and the artificial neural network (ANN) method. These methods allowed us to obtain three (3) quantitative models from the quantum descriptors that are, chemical potential (μ), polarizability (α), bond length l (C = N), and lipophilicity. These models showed good statistical performance. Among these, the ANN has a significantly better predictive ability R<sup>2</sup> = 0.9995;RMSE = 0.0149;F = 31879.0548. The external validation tests verify all the criteria of Tropsha et al. and Roy et al. Also, the internal validation tests show that the model has a very satisfactory internal predictive character and can be considered as robust. Moreover, the applicability range of this model determined from the levers shows that a prediction of the pMIC of the new benzimidazole derivatives is acceptable when its lever value is lower than 1.
文摘目的建立H37Rv结核分支杆菌诱导的兔脊柱结核模型。方法选择未致敏处理的新西兰大白兔48只,在第5腰椎近椎间盘处钻孔,并填充明胶海绵,注射0.5 mg/0.1 m L结核菌悬液,术后观察新西兰大白兔一般情况,并用影像学、组织病理学、细菌学等检查对兔脊柱结核模型进行评估。结果受H37Rv结核菌株感染后的新西兰大白兔,局部反应较明显,全身反应较轻。48只兔中38只兔完成实验,10只因死亡、术后截瘫被淘汰,15只兔分别于术后第5、6周出现进食欠佳、消瘦,但生命体征平稳,其中4只术区局部肿胀,6只出现下肢运动障碍;其余23只兔术后进食较好,体质量未见明显变化。术后3个月行外科手术,暴露致病兔椎体,38只兔中29只兔椎体可见虫噬样改变,9只兔椎体未见明显变化。术中取脓肿形成的兔脓液培养示结核分枝杆菌生长;取周围软组织、脓壁行苏木精-伊红色(HE)染色,示坏死灶形成、较多炎细胞聚集、淋巴细胞、较少上皮样细胞,骨结构紊乱或消失。建立模型成功率为76.3%(29/38)。结论使用0.5 mg/0.1 m L的H37Rv标准菌株感染的新西兰白兔结核模型建立成功。
