Computational Science Center, Future Fusion Technology Division, Korea Institute of Science and Technology, P.O. Box 131, Seoul 130-650, South Korea.
Environ Toxicol Pharmacol. 2008 Sep;26(2):128-35. doi: 10.1016/j.etap.2008.01.005. Epub 2008 Feb 1.
N-Phenyl benzamides are potent antibacterial agents. They are active against both Gram-positive and Gram-negative bacteria. The Gram-positive bacteria have strong and thick cell wall while the Gram-negative bacterial have thin and permeable cell wall. The DFT based QSAR reveals that molecular weight and total energy significantly contribute to activity against both kinds of target. The electrophilicity index involved in QSAR models derived with anti-Gram-positive activity indicates the dominance of electrostatic interaction. The molar refractivity and logP is involved in QSAR model derived with anti-Gram-negative activity shows steric and hydrophobic interaction. The CoMFA and CoMSIA results also indicate that anti-Gram-positive bacterial activity is a function of electrostatic field effect but the anti-Gram-negative activity depends on hydrophobicity and steric field effect. The CoMFA and CoMSIA contour maps give an indication, the electropositive group around benzene "X" and an electronegative group around carbonyl oxygen is desirable for better anti-Gram-positive bacterial activity. A hydrophobic group around meta position of ring "X" with bulky group at ortho position and a small group at para position are desirable for better activity against Gram-negative target. The findings are reasonable and the mechanism might be different due to difference in composition of cell wall. The cell wall of Gram-positive target does not allow the permeability and only external electrostatic interaction is possible while the cell wall of Gram-negative target allows the permeability of molecules inside the cell for possible hydrophobic and steric bulk interaction.
N-苯基苯甲酰胺是一种有效的抗菌剂。它们对革兰氏阳性菌和革兰氏阴性菌都有活性。革兰氏阳性菌的细胞壁又厚又强，而革兰氏阴性菌的细胞壁又薄又有渗透性。基于密度泛函理论的 QSAR 揭示了分子量和总能量对两种靶标活性的显著贡献。与抗革兰氏阳性活性相关的 QSAR 模型中的电负性指数表明静电相互作用占主导地位。与抗革兰氏阴性活性相关的 QSAR 模型中涉及的摩尔折射度和 logP 表明了立体和疏水性相互作用。CoMFA 和 CoMSIA 结果还表明，抗革兰氏阳性菌活性是静电场效应的函数，而抗革兰氏阴性菌活性取决于疏水性和立体场效应。CoMFA 和 CoMSIA 等高线图表明，苯环“X”周围带正电荷的基团和羰基氧周围带负电荷的基团有利于更好的抗革兰氏阳性菌活性。环“X”间位带有较大取代基和对位带有较小取代基的疏水区有利于更好地针对革兰氏阴性靶标发挥作用。这些发现是合理的，由于细胞壁成分的不同，其机制可能也不同。革兰氏阳性靶标的细胞壁不允许分子渗透，只有外部静电相互作用是可能的，而革兰氏阴性靶标的细胞壁允许细胞内分子的渗透，从而可能发生疏水和立体位阻相互作用。
