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Cytotoxicity of 3-(2-benzoxazol-5-yl)alanine derivatives

Ewa Mulkiewicz ,  Katarzyna Guzow ,  Wiesław Wiczk 

University of Gdańsk, Faculty of Chemistry, J. Sobieskiego 18, Gdańsk 80-952, Poland

Abstract

3-(2-benzoxazol-5-yl)alanine derivatives are a group of unnatural amino acids which can be used as fluorescent probes [1,2]. Moreover, some of them are active against Bacillus subtilis, Pichia pastoris, Candida albicans, Aspergillus niger [3]. Because of that, cytotoxicity of those compounds was studied using in vitro methods. Tests were performed for 40 derivatives using tumour cell lines (rat glial cells C6 and mouse fibroblasts A9) as well as normal cell line (embryonic kidney cells Hek 293). WST-1 test was used to determine concentrations of the compounds causing 50% reduction of the cells viability compared with control values (EC50) [4,5]. It was found that only 7 compounds among all studied are not toxic to the tumour rat glial cells (3-[2-(2-naphthyl)benzoxazol-5-yl]alanine, 3-[2-(4-biphenyl)benzoxazol-5-yl]alanine, 3-[2-(4-methylphenyl)benzoxazol-5-yl]alanine, 3-[2-(2-benzofuryl)benzoxazol-5-yl]alanine, 3-[2-(2,4-dihydroxyphenyl)benzoxazol-5-yl]alanine methyl ester, 3-[2-(4-carboxyphenyl)benzoxazol-5-yl]alanine methyl ester, 3-[2-(2-imidazolyl)benzoxazol-5-yl]alanine). In the case of Hek 293 cell line, only one compound among studied was not toxic - 3-[2-(4-phenylboronic acid)benzoxazol-5-yl]alanine methyl ester. For all cell lines studied, similar structure-activity relationship was observed. However, the mouse fibroblasts A9 were more sensitive to the presence of the compounds studied than rat glial cells C6. Also, in some cases of the compounds studied the hormetic effect was observed. Most of compounds studied was less toxic to the normal cell line in comparison with tumour cell lines, except for 3-[2-(8-quinolinyl)benzoxazol-5-yl]alanie methyl ester and 3-[2-(2,5-dimethoxyphenyl)benzoxazol-5-yl]alanine methyl ester which were more toxic. References: [1] K. Guzow, M. Szabelski, J. Karolczak, W. Wiczk, J. Photochem. Photobiol. A: Chem. 170 (2005) 215. [2] M. Szabelski, M. Rogiewicz, W. Wiczk, Anal. Biochem. 342 (2005) 20. [3] K. Guzow, M. Obuchowski, W. Wiczk, Acta Biochim. Pol. 53 (suppl) (2006) 184. [4] L. Ranke, K. Molter, F. Stock, U. Bottin-Weber, J. Poczobutt, J. Hoffmann, B. Ondruschka, J. Filser, B. Jastorff, Ecotoxicol. Environ. Saf. 58 (2004) 396. [5] P.H. Van Ewijk, J.A. Hoekstra, Ecotoxicol. Environ. Saf. 25 (1993) 25. Acknowledgement. This work was financially supported by the Polish Ministry of Science and Higher Education under grants BW 8000-5-0287-6 and BW 8000-5-0049-7.

 

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Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum V, by Katarzyna Guzow
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-05-06 22:05
Revised:   2009-06-07 00:44