Evaluation of lipophilicity and antitumour activity of parallel carboxamide libraries

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Abstract

Searching for molecules possessing antitumour activity, a parallel molecule library of aromatic carboxamides has been designed and synthesised. This work resulted in a “thiophene” sub-library containing a thiophene core and of a “furoyl” sub-library with a furoyl core, respectively. In both sub-libraries substitutions were carried out with six different groups resulting in six pairs of compounds differing in only the heteroatom of aromatic ring of the cores. To study the importance of the type of cores and the specific substitutions in relation to their lipophilicity and antitumour activity, lipophilicity of carboxamides was determined by chromatographical data (log k′) and by software calculated parameters (CLOGP). Pairs of compounds were tested for their ability to inhibit the proliferation of the A431 cells by MTT assay. The isosteric molecule pairs were successfully separated. Our results showed that the experimentally determined (log k′) and the calculated (CLOGP) lipophilicity parameters correlated well with each other. Furthermore, lipophilicity values of the thiophene sub-library were always higher than those in the furoyl sub-library. Moreover, compounds of the thiophene sub-library were more active than their respective furoyl pairs in our MTT antiproliferative assay. From these observations we can conclude that the higher the lipophilicity values the higher the antitumour activity of the carboxamides synthesised. Therefore, determination of lipophilicity by measuring the log k′ or by calculating the CLOGP values of the carboxamide sub-libraries may help to predict their biological activities.

Original languageEnglish
Pages (from-to)355-363
Number of pages9
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume780
Issue number2
DOIs
Publication statusPublished - Nov 25 2002

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Keywords

  • Carboxamide parallel library
  • Lipophilicity

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

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