M. Topashka-Ancheva, P. Todorov , Ts. Gerasimova, E. Naydenova 191 Journal of the University of Chemical Technology and Metallurgy, 46, 2, 2011, 191-196 GENOTOXIC AND ANTIPROLIFERATIVE EFFECTS OF RECENT SYNTHESIZED HYDANTOIN-PHOSPHONIC DERIVATIVES M. Topashka-Ancheva 1 , P . T odorov 2 , Ts. Gerasimova 1 , E. Naydenova 2 ABSTRACT The variety of biological activities expressed by aminophosphonic acids bearing hydantoin moiety is surprisingly high. Several applications, in quite different fields such as agriculture and human health, have been reported. This report refers to the investigation of genotoxic and antiproliferative effect of recently synthesized aminophosphonic acids with hydantoin moiety. These effects of the newly synthesized [(5,5-dimethyl-2,4-dioxoimidazolidine-1,3- diyl)dimethyl]diphosphonic acid (), dimethyl[(5,5-dimethyl-2,4-dioxoimidazolidin-3-yl)aminomethyl]phosphonate and dimethyl[(3-[(dimethoxy-phosphoryl)methyl]amino-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl)methyl]phosphonate " were investigated for the first time. They exhibited moderate clastogenicity, and high antiproliferative activity on ICR mice bone marrow cells. Keywords: aminophosphonic acids; hydantoin derivatives; chromosomal aberrations; cell proliferation; clastogenic effects. Received 15 March 2011 Accepted 26 May 2011 INTRODUCTION Aminophosphonates are valuable intermediates for the preparation of medicinal compounds and syn- thetic intermediates. In the past decades there has been an increasing interest in the study of phosphonic acids derivatives as stable mimetics of natural phosphates and substrates in the study of biochemical processes. In par- ticular, aminophosphonic acids derivatives are isosteres of the corresponding amino acids and exhibit a variety of important biological properties. Among these phos- phorus-containing compounds á-aminophosphonic ac- ids are the most attractive substances which possess a variety of biological activities. Furthermore, aminophosphonates have found a multitude of applica- tions in medicinal, agricultural, and industrial chemis- try. The established antiproliferative effects, together with the low mammalian toxicity of these agents, have con- 1 Institute of Biodiversity and Ecosystems Research, Bulgarian Academy of Sciences, 1 “Tzar Osvoboditel”, Sofia 1000, Bulgaria 2 University of Chemical Technology and Metallurgy 8 Kl. Ohridski, 1756 Sofia, Bulgaria E-mail: pepi_37@abv.bg ditioned tremendous interest towards designing novel antineoplastic agents [1-6]. á-Aminophosphonates are chief substrates also in the synthesis of phosphonopeptides. Due to their structural analogy with á-amino acids, these types of organophosphorus com- pounds are widely used for the development of new in- hibitors of enzymes, neuroactive compounds, and plant growth regulators. Numerous phosphonopeptides pos- sess antibacterial and effective inhibitor activity against different kind of tumors, leukemia, multiple sclerosis and autoimmune diseases [1,2]. Synthesis of aminophosphonic acids is an active area of research, and many methods are now available [7-12]. Among the number of synthetic approaches to á-aminophosphonates, one of the most powerful meth- ods is the Kabachnik-Fields reaction [13-15]. This reli- able method for the synthesis of aminophosphonates is the three component reaction that occurs when a car-