Jesudason E Philip, Sridhar S K, Malar E J Padma, Shanmugapandiyan P, Inayathullah Mohammed, Arul V, Selvaraj D, Jayakumar R
Bio-Organic and Neurochemistry Laboratory, Central Leather Research Institute, Sardar Patel Road, Adyar, Chennai 600020, Tamil Nadu, India.
Eur J Med Chem. 2009 May;44(5):2307-12. doi: 10.1016/j.ejmech.2008.03.043. Epub 2008 Apr 11.
A novel series of N-Mannich bases of benzimidazole derivatives were synthesized and characterized by (1)H NMR, IR spectral studies and elemental analysis. The compounds were screened for analgesic and anti-inflammatory activity. 1-((Diethylamino)-methyl)-2-styryl benzimidazole 4 at 40mg/kg was found to be equipotent to paracetamol. 1-((Piperidin-1-yl) methyl)-2-styryl-benzimidazole 6 at 40mg/kg was found to be more potent than Diclofenac. Corneal permeability and quantum chemical calculations were performed to correlate the hydrogen bonding ability with permeability and activity. The energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were correlated with pharmacological activity. The semi-empirical PM3 calculations (quantum chemical calculations) revealed that E(LUMO) and energy gap DeltaE were capable of accounting for the high in vitro bovine corneal permeability and activity of the compounds.
合成了一系列新型的苯并咪唑衍生物的N-曼尼希碱，并通过¹H NMR、红外光谱研究和元素分析对其进行了表征。对这些化合物进行了镇痛和抗炎活性筛选。发现1-((二乙氨基)-甲基)-2-苯乙烯基苯并咪唑4在40mg/kg时与扑热息痛等效。发现1-((哌啶-1-基)甲基)-2-苯乙烯基苯并咪唑6在40mg/kg时比双氯芬酸更有效。进行了角膜通透性和量子化学计算，以将氢键能力与通透性和活性相关联。最高占据分子轨道(HOMO)和最低未占据分子轨道(LUMO)的能量与药理活性相关。半经验PM3计算(量子化学计算)表明，E(LUMO)和能隙ΔE能够解释这些化合物的高体外牛角膜通透性和活性。
