Investigation of lipophilicity of anticancer-active thioquinoline derivatives.
The lipophilicity of a series of anticancer propargylthioquinoline derivatives has been investigated using chromatographic and computational methods. The parameters of relative lipophilicity (R(MO) and logk0) of the tested compounds were determined experimentally both by reversed-phase thin layer (RP-TLC), and high-performance liquid chromatographic methods (RP-HPLC, LiChrospher RP18 column), with mixtures of acetonitrile and water as mobile phases. Their phospholipophilicity (logk(0IAM)) was determined using immobilized artificial membrane HPLC (IAM. PC DD2 Regis column). Mobile phase acetonitrile concentrations were in the ranges 50-90% (RP-TLC), 55-90% (RP-HPLC) and 35-60% (IAM-HPLC). The R(M), logk and logk(IAM) values of the compounds investigated were linearly dependent on acetonitrile concentration. The analysis led to the calculation of R(MO), logk0 and logk(0IAM) parameter values for each of the tested compounds. Their partition coefficients (logP) were also calculated with the Pallas and CAChe programs. The obtained results indicated that, among experimental methods, both RP-TLC and RP-HPLC gave similar results, and these methods enable the determination of lipophilicity of derivatives of thioquinolines. Using the IAM-HPLC technique a simple method of estimation of phospholipoplilicity was described. The CAChe program might better predict calculated lipophilicity logP values, and therefore is a useful tool for the early stage of design of new propargyl thioquinolines.
Bajda
Marek
M
Department of Physicochemical Drug Analysis, Jagiellonian University, Medical College, 9 Medyczna St, 30-688 Kraków, Poland.
Boryczka
Stanisław
S
Wietrzyk
Joanna
J
Malawska
Barbara
B
D000097:Acetonitriles / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D008055:Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000737:chemistry*; D012984:Software; D012995:Solubility
D000097:Acetonitriles; D000970:Antineoplastic Agents; D008055:Lipids; D008567:Membranes, Artificial; D011804:Quinolines; C032159:acetonitrile