Search for content and authors
 

INVESTIGATIONS OF LIPOPHILICITY OF ANTICANCER-ACTIVE THIOQUINOLINE DERIVATIVES

Barbara Malawska 1Marek Bajda 1Stanisław Boryczka 2

1. Jagiellonian University, Collegium Medicum, Department of Pharmaceutical Chemistry, Medyczna 9, Kraków 30-688, Poland
2. Medical University of Silesia, Department of Organic Chemistry, Jagiellonska 4, Sosnowiec 41-200, Poland

Abstract

The biological activity of molecules is related to their chemical structure and physicochemical properties. It is well known that lipophilicity plays an important role in several aspects of absorption, distribution, metabolism, and excretion (ADME) of compounds [1-3]. The aim of our study was the estimation of the lipophilicity of propargyl thioquinolines, and search for relationships between their lipophilicity and in vitro anticancer activity. The synthesis of propargyl thioquinolines and thier antiproliferative activity against the breast line T47D have been described previously [4]. The lipophilicity of the series of the anticancer propargyl thioquinoline derivatives has been investigated using chromatograhic and computational methods. The parameters of relative lipophilicity (RMO and log k') of the tested compounds was determined experimentally both by reverse-phase thin layer (RP-TLC), and high performance liquid chromatographic methods (RP-HPLC, LiChrospher RP-18 column), with mixtures of acetonitile and water as mobile phases. Their phospholipophilicity (log k'IAM ) was determined using immobilized artificial membrane HPLC (IAM.PC DD2 Regis column). Acetonitrile in mobile phases was used in the concentrations: 50-90% (RP-TLC), 55-90% (RP-HPLC) and 35-60% (IAM-HPLC). The RM, log k and log kIAM values of the investigated compounds were linearly dependent on the acetonitrile concentration. The analysis allowed us to calculate the parameters: RMO, log k' and log k'IAM values for each of the tested compounds. Their partition coefficients (log P) were also calculated with the Pallas (ver. 1.2 Compu Drug Chemistry Ltd, 1995) and CAChe (6.1.10) programs. The experimental and theoretical data has been compared and the relationship between the structure and the lipophilicity has been found. The quantitative structure-activity relationship studies have indicated that for the tested compounds there are dependencies between their lipophilicity and in vitro anticancer activity, expressed as ID50 [mg mL-1], against the breast cancer cell line (T47D).

1. Gensmantel N.P. Physicochemical Properties and Drug Design, in King F.D. (Ed.) Medicinal Chemistry: Principles and Practice, Royal Society of Chemistry, Cambridge, 2001, 98.
2. Kansy M., Fischer H., Kratzat K., Senne F., Wagner B., Parrilla I., High-throughput artificial membrane permeability studies in early lead discovery and development. in Pharmacokinetic Optimization in Drug Research, Testa B., van de Waterbeemd H., Folkers G., Guy R. (Ed.) Wiley-VCH, 2001, 447.
3. Li AP. In vitro approaches to evaluate ADMET drug properties. Curr. Top. Med. Chem. 2004, 4, 701.
4. Boryczka S., Wietrzyk J., Opolski A. Synthesis and antiproliferative activity in vitro of new propargyl thioquinolines. Pharmazie, 57, 2002, 151.
 

Legal notice
  • Legal notice:
 

Related papers

Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Barbara Malawska
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-02-28 17:41
Revised:   2009-06-07 00:44