Altomare C, Tsai R S, el Tayar N, Testa B, Carotti A, Cellamare S, De Benedetti P G
Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Switzerland.
J Pharm Pharmacol. 1991 Mar;43(3):191-7. doi: 10.1111/j.2042-7158.1991.tb06664.x.
The lipophilic character of two large series of substituted benzenesulphonamides (BzSA) and 4-aminodiphenylsulphones (4-ADS) has been assessed by two chromatographic methods, i.e. reversed-phase HPLC using a relatively novel octadecylpolyvinyl packing and centrifugal counter-current chromatography (CPC). The octadecylpolyvinyl stationary phase proved an interesting alternative to the more common octadecylsilane type stationary phase for obtaining retention parameters correlated to partition coefficients (i.e. log P). The CPC method, being far less time-consuming and markedly more precise than the classical shake-flask method, offers a promising alternative for measuring partition coefficients. The parameter delta log Poct-hep, i.e. log Poctanol minus log Pheptane, was also determined for both congeneric series and was indicative of a similar H-bonding capacity for the SO2NH2 and 4-NH2-C6H4-SO2 groups. QSAR analyses of carbonic anhydrase inhibition by BzSA and antimycobacterial activity of 4-ADS show the capacity of the new lipophilicity parameters to express the hydrophobic component of the drug-enzyme interactions and to reveal a possible role of H-bond donor capacity in governing the antimycobacterial activity of 4-ADS.
通过两种色谱方法评估了两大系列取代苯磺酰胺（BzSA）和4-氨基二苯砜（4-ADS）的亲脂性，即使用相对新颖的十八烷基聚乙烯填料的反相高效液相色谱法和离心逆流色谱法（CPC）。对于获得与分配系数（即log P）相关的保留参数而言，十八烷基聚乙烯固定相被证明是比更常见的十八烷基硅烷型固定相更有趣的替代物。CPC方法比经典的摇瓶法耗时少得多且明显更精确，为测量分配系数提供了一种有前景的替代方法。还针对这两个同系物系列测定了参数δlog Poct-hep，即log Poctanol减去log Pheptane，它表明SO2NH2和4-NH2-C6H4-SO2基团具有相似的氢键结合能力。对BzSA抑制碳酸酐酶和4-ADS抗分枝杆菌活性的定量构效关系分析表明，新的亲脂性参数能够表达药物与酶相互作用的疏水成分，并揭示氢键供体能力在控制4-ADS抗分枝杆菌活性中可能发挥的作用。
