Deguanylation of Guanine Based-Nucleosides and Calf Thymus DNA Induced by Halogenated Alkanes at the Physiological Condition

Sherchan, Jyoti,Lee, Eung-Seok Korean Chemical Society 2009 Bulletin of the Korean Chemical Society Vol.30 No.12

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$^{\circ}C$), 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.

Deadenylation of Adenine Based-Nucleosides and Calf thymus DNA Induced by Halogenated Alkanes at the Physiological Condition

Sherchan, Jyoti,Yun, Min-Ho,Lee, Eung-Seok Korean Chemical Society 2009 Bulletin of the Korean Chemical Society Vol.30 No.10

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, $37\;{^{\circ}C}$), 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.

Depurination of Nucleosides and Calf Thymus DNA Induced by 2-Bromopropane at the Physiological Condition

Sherchan, Jyoti,Choi, Ho-Young,Lee, Eung-Seok Korean Chemical Society 2009 Bulletin of the Korean Chemical Society Vol.30 No.10

Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though 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 replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though $N^7$-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.

Deguanylation of Guanine Based-Nucleosides and Calf Thymus DNA Induced by Halogenated Alkanes at the Physiological Condition

Jyoti Sherchan,Eung-Seok Lee 대한화학회 2009 Bulletin of the Korean Chemical Society Vol.30 No.12

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 oC), 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.

Deadenylation of Adenine Based-Nucleosides and Calf thymus DNA Induced by Halogenated Alkanes at the Physiological Condition

Jyoti Sherchan,Minho Yun,Eung-Seok Lee 대한화학회 2009 Bulletin of the Korean Chemical Society Vol.30 No.10

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 °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.

Depurination of Nucleosides and Calf Thymus DNA Induced by 2-Bromopropane at the Physiological Condition

Jyoti Sherchan,Hoyoung Choi,Eung-Seok Lee 대한화학회 2009 Bulletin of the Korean Chemical Society Vol.30 No.10

Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though 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 replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though N7-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, 37°C ), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.

Depurination of dA and dG Induced by 2-bromopropane at the Physiological Condition

Thapa, Pritam,Sherchan, Jyoti,Karki, Radha,Jeong, Tae-Cheon,Lee, Eung-Seok The Korean Society of Applied Pharmacology 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol. No.

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, $37^{\circ}C$), 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.

Synthesis, Cytotoxicity and Structure-Activity Relationship Study of Terpyridines

Long-Xuan Zhao,Jyoti Sherchan,Jung Ki Park,장영동,정병선,정태천,이종순,이응석 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.12

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.

Synthesis, Cytotoxicity and Structure-Activity Relationship Study of Terpyridines

Zhao, Long-Xuan,Sherchan, Jyoti,Park, Jung-Ki,Jahng, Yurng-Dong,Jeong, Byeong-Seon,Jeong, Tae-Cheon,Lee, Chong-Soon,Lee, Eung-Seok The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.12

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 of dA and dG Induced by 2-bromopropane at the Physiological Condition

( Pritam Thapa ),( Jyoti Sherchan ),( Radha Karki ),( Tae Cheon Jeong ),( Eung Seok Lee ) 한국응용약물학회 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol.15 No.4

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℃), 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.