Determination of lipophilicity and hydrogen-bond donor acidity of bioactive sulphonyl-containing compounds by reversed-phase HPLC and centrifugal partition chromatography and their application to structure-activity relations.
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.
Altomare
C
C
Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Switzerland.
Tsai
R S
RS
el Tayar
N
N
Testa
B
B
Carotti
A
A
Cellamare
S
S
De Benedetti
P G
PG
D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis; D002498:Centrifugation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002845:Chromatography; D002851:Chromatography, High Pressure Liquid; D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors; D006859:Hydrogen / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
D002257:Carbonic Anhydrase Inhibitors; D008055:Lipids; D013449:Sulfonamides; D006859:Hydrogen; D004094:Dihydropteroate Synthase