For the development of novel antitumor agents, we designed and synthesized terpyridines, and their biological activities were evaluated. Although most of the newly prepared terpyridines showed strong cytotoxicity against several human cancer cell lines, [2,2';6',2"]-terpyridine displayed the most significant cytotoxicity.
− Depurination, the release of purine bases from nucleosides by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Although, cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a cleaning solvent in electronics industry. But, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. We observed massive depurination after incubation of 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) with the excess amount 2-BP at the physiological condition (pH 7.4, 37 o C), which were analyzed by HPLC and LC-MS/MS. In addition, time and dose response relationship of depurination in dA and dG induced by 2-BP at the physiological condition were investigated.
Massive deguanylation of guanine based-nucleosides induced by halogenated alkanes at the physiological condition have been observed. For the study of deguanylation effects by the different substituents and/or functionality in halogenated alkanes, diverse kinds of halogenated alkanes were incubated with guanine based-nucleosides (ddG, dG and guanosine) for 48 h at the physiological condition (pH 7.4, 37 o C), which were analyzed by HPLC and further confirmed by LC-MS. Among the sixteen different halogenated alkanes, we observed massive deguanylation of nucleosides by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. The order of deguanylation rate was highest in 2-bromo-2-methylpropane followed by 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. In addition, time and dose response relationship of deguanylation in guanine basednucleosides induced by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane at the physiological condition were investigated. Deguanylation of calf thymus DNA induced by halogenated alkanes was also investigated. These results suggest that the toxic effect of certain halogenated alkanes might be from the depurination of nucleosides.
Massive deadenylation of adenine based-nucleosides induced by halogenated alkanes at the physiological condition have been observed. For the study of deadenylation effects by the different substituents and/or functionality in halogenated alkanes, diverse kinds of halogenated alkanes were incubated with adenine based-nucleosides (ddA, dA and adenosine) for 48 h at the physiological condition (pH 7.4, 37 o C), which were analyzed by HPLC and further confirmed by LC-MS. Among the sixteen different halogenated alkanes, we observed massive deadenylation of nucleosides by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. The order of deadenylation rate was highest in 2-bromo-2-methylpropane followed by 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. In addition, time and dose response relationship of deadenylation in adenine based-nucleosides induced by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane at the physiological condition were investigated. In addition, deadenylation of calf thymus DNA induced by halogenated alkanes was also investigated. These results suggest that the toxic effect of certain halogenated alkanes might be from the depurination of nucleosides.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.