Abstract

Recently, much attention has been directed to the synthesis of phosphorus heterocycles. Here we wish to report our results on synthesis and on studying of biological activity of 4-bromo-5-ethyl-2-(ethylamino)-5-methyl-5H-1,2-oxaphosphole 2-oxide (Br-oxph-1) using in vivo and in vitro approaches. Br-oxph-1 represents a structural analogue of 4-bromo-2-(diethylamino)-5-ethyl-5-methyl-5H-1,2-oxaphosphole 2-oxide (Br-oxph). Root growth inhibition test using Triticum aestivum L. seeds was provided in order to determine general toxicity of Br-oxph-1. The effective concentration that cause 50% of root length as compared to control was determined – 8.23×103 μM. Cytotoxic potential of Br-oxph-1 (8.23×103 μM) was evaluated using Allium cepa L.-test. Significant decline in mitotic activity and disturbances of cell cycle kinetics were observed. Further, effects of Br-oxph-1 on human hepatoma cell line SK-HEP-1 in vitro were evaluated by means of cell proliferation assay. The results revealed concentration-dependent and statistically significantinhibitory effect. Concentration of Br-oxph-1 showing 50% reduction in cell proliferation/viability was 0.642×103 µM. In conclusion, plant test-systems used in this study revealed growth inhibitory and cytostatic effects of Br-oxph-1. Data in vitro was in accordance with these results. Results of present study revealed stronger cytostatic effect of Br-oxph-1 in comparison with Br-oxph. Obviously, modifications in chemical structure of Br-oxph influence its biological effects.

Key words: 4-bromo-5-ethyl-2-(ethylamino)-5-methyl-5H-1,2-oxaphosphole 2-oxide, Cytotoxicity, Allium cepa L.-test, WST-1 cell proliferation/viability assay, Cancer cells