Collect. Czech. Chem. Commun.
2002, 67, 257-266
https://doi.org/10.1135/cccc20020257
Effect of the Purine Derivative Myoseverin and of Its Analogues on Cultured Hybridoma Cells
František Franěka,*, Věra Siglerováb, Libor Havlíčekb, Miroslav Strnadc, Tomáš Eckschlagerd and Evžen Weigle
a Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Radiová 1, 102 27 Prague 10, Czech Republic
b Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic
c Laboratory of Growth Regulators, Institute of Experimental Botany, Academy of Sciences of the Czech Republic and Palacký University, Šlechtitelů 11, 783 71 Olomouc, Czech Republic
d Department of Pediatric Oncology, 2nd Medical Faculty, Charles University, V Úvalu 84, 150 06 Prague 5, Czech Republic
e Department of Immunology, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic
Abstract
Two 2,6,9-trisubstituted purine derivatives, 9-isopropyl-2,6-bis[(4-methoxybenzyl)amino]-9H-purine (myoseverin, PMYO, 1) and 9-isopropyl-2,6-bis[(2-methoxybenzyl)amino]-9H-purine (OMYO, 2), and two 6,9-disubstituted derivatives, 9-isopropyl-6-[(4-methoxybenzyl)amino]-9H-purine (3) and 9-isopropyl-6-[(2-methoxybenzyl)amino]-9H-purine (4), were synthesized with the aim to examine their cell proliferation inhibiting activity, and possible additional effects in cultures of hybridoma cells producing monoclonal antibody. The substances were tested over a concentration range from 0.003 to 30 μmol l-1. The most active compound 1 caused a total loss of cell viability at 1 μmol l-1, while its isomer 2 showed the same effect at 10 μmol l-1 concentration. In the presence of compound 1, but not of compound 2, the character of the cell cycle phases profile changed dramatically, most cells being arrested in the G2/M phase. At intermediate concentrations of compound 2 a substantially higher viable cell concentration was observed, relative to control. These differences demonstrated the principal significance of the position of the methoxy groups on the benzene rings for the biological effect. The 6,9-disubstituted derivatives 3 and 4 were without significant effect in the whole range of concentrations tested. The enhancement of monoclonal antibody production, observed in certain concentration intervals of added substances, was of marginal character.
Keywords: Purines; CDK Inhibitors; Cytokinins; Cytostatics; Hybridoma cells; Monoclonal antibodies.
References: 19 live references.
