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Lak Shin Jeong - One of the best experts on this subject based on the ideXlab platform.
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STRUCTURE-ACTIVITY RELATIONSHIP OF 5′-SUBSTITUTED FLUORO-NeplAnocin A ANALOGUES AS POTENT INHIBITORS OF S-ADENOSYLHOMOCYSTEINE HYDROLASE
Nucleosides Nucleotides & Nucleic Acids, 2020Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Seung Bin Park, Lak Shin JeongAbstract:Four 5′-substituted fluoro-NeplAnocin A AnAlogues 1A–d were designed And synthesized, And the inhibitory Activity AgAinst SAH wAs in the following order: NH2 > SH > F, N3, indicAting A hydrogen bonding donor is essentiAl for inhibitory Activity.
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AntiproliferAtive And AntimigrAtion Activities of fluoro NeplAnocin A viA inhibition of histone h3 methylAtion in triple negAtive breAst cAncer
Biomolecules, 2020Co-Authors: Woong Sub Byun, Jiseong Yoon, Dnyandev B Jarhad, Lak Shin JeongAbstract:Triple-negAtive breAst cAncer (TNBC) is Among the most Aggressive And potentiAlly metAstAtic mAlignAncies. Most Affected pAtients hAve poor clinicAl outcomes due to the lAck of specific moleculAr tArgets on tumor cells. The upregulAted expression of disruptor of telomeric silencing 1-like (DOT1L), A histone methyltrAnsferAse specific for the histone H3 lysine 79 residue (H3K79), is strongly correlAted with TNBC cell Aggressiveness. Therefore, DOT1L is considered A potentiAl moleculAr tArget in TNBC. Fluoro-NeplAnocin A (F-NepA), An inhibitor of S-Adenosylhomocysteine hydrolAse, exhibited potent AntiproliferAtive Activity AgAinst vArious types of cAncer cells, including breAst cAncers. However, the moleculAr mechAnism underlying the AnticAncer Activity of F-NepA in TNBC cells remAins to be elucidAted. We determined thAt F-NepA exhibited A higher growth-inhibitory Activity AgAinst TNBC cells relAtive to non-TNBC breAst cAncer And normAl breAst epitheliAl cells. Moreover, F-NepA effectively downregulAted the level of H3K79me2 in MDA-MB-231 TNBC cells by inhibiting DOT1L Activity. F-NepA Also significAntly inhibited TNBC cell migrAtion And invAsion. These Activities of F-NepA might be AssociAted with the upregulAtion of E-cAdherin And downregulAtion of N-cAdherin And Vimentin in TNBC cells. TAken together, these dAtA highlight F-NepA As A strong potentiAl cAndidAte for the tArgeted treAtment of high-DOT1L-expressing TNBC.
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An efficient synthesis of fluoro NeplAnocin A AnAlogs using electrophilic fluorinAtion And pAllAdium cAtAlyzed dehydrosilylAtion
Organic chemistry frontiers, 2019Co-Authors: Dnyandev B Jarhad, Min Hwan Jang, Young Sup Shin, Young Eum Hyun, Jiseong Yoon, Lak Shin JeongAbstract:NeplAnocin A AnAlogs hAve AttrActed Attention in the fields of biologicAl And medicinAl chemistry due to their potent And broAd-spectrum AntivirAl And Antitumor Activities. To further explore their potentiAl As therApeutic Agents, An AlternAtive And efficient synthesis of fluoro-NeplAnocin A AnAlogs hAs been developed by employing stereoselective electrophilic fluorinAtion And pAllAdium-cAtAlyzed dehydrosilylAtion As key steps. With respect to previous syntheses, the present synthetic methodology provides eAsy Access to key intermediAtes thAt could contribute to expAnding further the structure–Activity relAtionship studies of NeplAnocin A AnAlogs.
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structure Activity relAtionship of 5 substituted fluoro NeplAnocin A AnAlogues As potent inhibitors of s Adenosylhomocysteine hydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2005Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Seung Bin Park, Lak Shin JeongAbstract:Four 5′-substituted fluoro-NeplAnocin A AnAlogues 1A–d were designed And synthesized, And the inhibitory Activity AgAinst SAH wAs in the following order: NH2 > SH > F, N3, indicAting A hydrogen bonding donor is essentiAl for inhibitory Activity.
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synthesis of 5 substituted fluoro NeplAnocin A AnAlogues importAnce of A hydrogen bonding donor At 5 position for the inhibitory Activity of s Adenosylhomocysteine hydrolAse
Bioorganic & Medicinal Chemistry Letters, 2004Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Lak Shin JeongAbstract:AbstrAct Four 5′-substituted fluoro-NeplAnocin A AnAlogues 1A – d were designed And synthesized, using cyclopentenone derivAtive 2 As A key intermediAte. The inhibitory Activity AgAinst SAH wAs in the following order: NH 2 > SH > F, N 3 , indicAting A hydrogen bonding donor such As OH or NH 2 wAs essentiAl for inhibitory Activity. All the finAl compounds showed much less decreAsed cytotoxicity in two cAncer cell lines (Col2 And A549), implying thAt phosphorylAtion of the 5′-hydroxyl group of fluoro-NeplAnocin A is closely relAted to its high cytotoxicity.
Hiromichi Tanaka - One of the best experts on this subject based on the ideXlab platform.
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rAdicAl mediAted stAnnylAtion of vinyl sulfones Access to novel 4 modified NeplAnocin A AnAlogues
Tetrahedron, 2009Co-Authors: Hiroki Kumamoto, Kazuki Deguchi, Yukio Kitade, Tadashi Wagata, Yuu Furuya, Yuki Odanaka, Hiromichi TanakaAbstract:AbstrAct Synthesis of 4′-substituted (hAlogeno, phenyl, ethynyl, And cyAno) NeplAnocin A AnAlogues wAs cArried out. A cyclopentenol derivAtive hAving A vinylstAnnAne structure wAs designed As key-intermediAte in this study, which wAs prepAred bAsed on rAdicAl-mediAted sulfur-extrusive stAnnylAtion. The resulting stAnnylAted cyclopentenol 15 wAs successfully condensed with 6-chloropurine through the Mitsunobu reAction, leAding to the cArbocyclic nucleoside 20 . Compound 20 wAs converted to its Adenine counterpArt 21 by treAtment with NH 3 /MeOH, during which the 4′-stAnnyl group remAined intAct. The title compounds were prepAred by using 21 or the 4′-iodo derivAtive ( 22 ) mostly through the Stille reAction.
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RAdicAl-mediAted stAnnylAtion of vinyl sulfones: Access to novel 4′-modified NeplAnocin A AnAlogues
Tetrahedron, 2009Co-Authors: Hiroki Kumamoto, Kazuki Deguchi, Yukio Kitade, Tadashi Wagata, Yuu Furuya, Yuki Odanaka, Hiromichi TanakaAbstract:AbstrAct Synthesis of 4′-substituted (hAlogeno, phenyl, ethynyl, And cyAno) NeplAnocin A AnAlogues wAs cArried out. A cyclopentenol derivAtive hAving A vinylstAnnAne structure wAs designed As key-intermediAte in this study, which wAs prepAred bAsed on rAdicAl-mediAted sulfur-extrusive stAnnylAtion. The resulting stAnnylAted cyclopentenol 15 wAs successfully condensed with 6-chloropurine through the Mitsunobu reAction, leAding to the cArbocyclic nucleoside 20 . Compound 20 wAs converted to its Adenine counterpArt 21 by treAtment with NH 3 /MeOH, during which the 4′-stAnnyl group remAined intAct. The title compounds were prepAred by using 21 or the 4′-iodo derivAtive ( 22 ) mostly through the Stille reAction.
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synthesis of novel 4 modified NeplAnocin A AnAlogues And their inhibitory Activity AgAinst s Adenosyl l l homocysteine hydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2007Co-Authors: Hiroki Kumamoto, Hiromichi Tanaka, Kazuki Deguchi, Nonoko Takahashi, Yukio KitadeAbstract:A new ApproAch wAs developed for the synthesis of 4′-modified NeplAnocin A AnAlogues, As potentiAl inhibitors AgAinst S-Adenosyl-L-homocysteine hydrolAse. The vinylstAnnAne 13, A key intermediAte in the present ApproAch, wAs prepAred by rAdicAl-mediAted sulfur-extrusive stAnnylAtion.
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Synthesis Of Novel 4′-Modified NeplAnocin A AnAlogues And Their Inhibitory Activity AgAinst S-Adenosyl-L-l-Homocysteine HydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2007Co-Authors: Hiroki Kumamoto, Hiromichi Tanaka, Kazuki Deguchi, Nonoko Takahashi, Yukio KitadeAbstract:A new ApproAch wAs developed for the synthesis of 4′-modified NeplAnocin A AnAlogues, As potentiAl inhibitors AgAinst S-Adenosyl-L-homocysteine hydrolAse. The vinylstAnnAne 13, A key intermediAte in the present ApproAch, wAs prepAred by rAdicAl-mediAted sulfur-extrusive stAnnylAtion.
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synthesis of 5 brAnched NeplAnocin A AnAlogues bAsed on rAdicAl mediAted sulfur extrusive stAnnylAtion
Nucleic acids symposium series (2004), 2007Co-Authors: Hiroki Kumamoto, Hiromichi TanakaAbstract:: An ApproAch wAs developed for the synthesis of 5'-brAnched NeplAnocin A, As potentiAl inhibitors AgAinst S-Adenosyl-L-homocysteine hydrolAse. The vinyl-stAnnAne system of the key synthetic intermediAte (14) in the present study, wAs prepAred by rAdicAl-mediAted sulfur-extrusive stAnnylAtion.
Moon Woo Chun - One of the best experts on this subject based on the ideXlab platform.
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STRUCTURE-ACTIVITY RELATIONSHIP OF 5′-SUBSTITUTED FLUORO-NeplAnocin A ANALOGUES AS POTENT INHIBITORS OF S-ADENOSYLHOMOCYSTEINE HYDROLASE
Nucleosides Nucleotides & Nucleic Acids, 2020Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Seung Bin Park, Lak Shin JeongAbstract:Four 5′-substituted fluoro-NeplAnocin A AnAlogues 1A–d were designed And synthesized, And the inhibitory Activity AgAinst SAH wAs in the following order: NH2 > SH > F, N3, indicAting A hydrogen bonding donor is essentiAl for inhibitory Activity.
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structure Activity relAtionship of 5 substituted fluoro NeplAnocin A AnAlogues As potent inhibitors of s Adenosylhomocysteine hydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2005Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Seung Bin Park, Lak Shin JeongAbstract:Four 5′-substituted fluoro-NeplAnocin A AnAlogues 1A–d were designed And synthesized, And the inhibitory Activity AgAinst SAH wAs in the following order: NH2 > SH > F, N3, indicAting A hydrogen bonding donor is essentiAl for inhibitory Activity.
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synthesis of 5 substituted fluoro NeplAnocin A AnAlogues importAnce of A hydrogen bonding donor At 5 position for the inhibitory Activity of s Adenosylhomocysteine hydrolAse
Bioorganic & Medicinal Chemistry Letters, 2004Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Lak Shin JeongAbstract:AbstrAct Four 5′-substituted fluoro-NeplAnocin A AnAlogues 1A – d were designed And synthesized, using cyclopentenone derivAtive 2 As A key intermediAte. The inhibitory Activity AgAinst SAH wAs in the following order: NH 2 > SH > F, N 3 , indicAting A hydrogen bonding donor such As OH or NH 2 wAs essentiAl for inhibitory Activity. All the finAl compounds showed much less decreAsed cytotoxicity in two cAncer cell lines (Col2 And A549), implying thAt phosphorylAtion of the 5′-hydroxyl group of fluoro-NeplAnocin A is closely relAted to its high cytotoxicity.
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synthesis And biologicAl evAluAtion of hAlo NeplAnocin A As novel mechAnism bAsed inhibitors of s Adenosylhomocysteine hydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2003Co-Authors: Lak Shin Jeong, Won Jun Choi, Hyung Ryong Moon, Jae Gyu Park, Dae Hong Shin, Moon Woo ChunAbstract:AbstrAct HAlogenAted AnAlogues of NeplAnocin A were synthesized from the key intermediAte 1, Among which fluoro-NeplAnocin A wAs found to be novel mechAnism-bAsed irreversible inhibitor of S-Adenosylhomocysteine hydrolAse.
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design synthesis And in vitro evAluAtion of Apio AnAlogue of NeplAnocin A
Nucleosides Nucleotides & Nucleic Acids, 2003Co-Authors: Hyung Ryong Moon, Moon Woo Chun, Sung Hee Kwon, Lak Shin JeongAbstract:AbstrAct A novel Apio AnAlogue of NeplAnocin A wAs efficiently synthesized from D-ribose viA stereoselective Aldol-retroAldol reAction for introducing hydroxymethyl group And RCM reAction for synthesizing cArbocycle, And its inhibitory Activity AgAinst SAH hydrolAse wAs AssAyed.
Hiroki Kumamoto - One of the best experts on this subject based on the ideXlab platform.
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rAdicAl mediAted stAnnylAtion of vinyl sulfones Access to novel 4 modified NeplAnocin A AnAlogues
Tetrahedron, 2009Co-Authors: Hiroki Kumamoto, Kazuki Deguchi, Yukio Kitade, Tadashi Wagata, Yuu Furuya, Yuki Odanaka, Hiromichi TanakaAbstract:AbstrAct Synthesis of 4′-substituted (hAlogeno, phenyl, ethynyl, And cyAno) NeplAnocin A AnAlogues wAs cArried out. A cyclopentenol derivAtive hAving A vinylstAnnAne structure wAs designed As key-intermediAte in this study, which wAs prepAred bAsed on rAdicAl-mediAted sulfur-extrusive stAnnylAtion. The resulting stAnnylAted cyclopentenol 15 wAs successfully condensed with 6-chloropurine through the Mitsunobu reAction, leAding to the cArbocyclic nucleoside 20 . Compound 20 wAs converted to its Adenine counterpArt 21 by treAtment with NH 3 /MeOH, during which the 4′-stAnnyl group remAined intAct. The title compounds were prepAred by using 21 or the 4′-iodo derivAtive ( 22 ) mostly through the Stille reAction.
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RAdicAl-mediAted stAnnylAtion of vinyl sulfones: Access to novel 4′-modified NeplAnocin A AnAlogues
Tetrahedron, 2009Co-Authors: Hiroki Kumamoto, Kazuki Deguchi, Yukio Kitade, Tadashi Wagata, Yuu Furuya, Yuki Odanaka, Hiromichi TanakaAbstract:AbstrAct Synthesis of 4′-substituted (hAlogeno, phenyl, ethynyl, And cyAno) NeplAnocin A AnAlogues wAs cArried out. A cyclopentenol derivAtive hAving A vinylstAnnAne structure wAs designed As key-intermediAte in this study, which wAs prepAred bAsed on rAdicAl-mediAted sulfur-extrusive stAnnylAtion. The resulting stAnnylAted cyclopentenol 15 wAs successfully condensed with 6-chloropurine through the Mitsunobu reAction, leAding to the cArbocyclic nucleoside 20 . Compound 20 wAs converted to its Adenine counterpArt 21 by treAtment with NH 3 /MeOH, during which the 4′-stAnnyl group remAined intAct. The title compounds were prepAred by using 21 or the 4′-iodo derivAtive ( 22 ) mostly through the Stille reAction.
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synthesis of novel 4 modified NeplAnocin A AnAlogues And their inhibitory Activity AgAinst s Adenosyl l l homocysteine hydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2007Co-Authors: Hiroki Kumamoto, Hiromichi Tanaka, Kazuki Deguchi, Nonoko Takahashi, Yukio KitadeAbstract:A new ApproAch wAs developed for the synthesis of 4′-modified NeplAnocin A AnAlogues, As potentiAl inhibitors AgAinst S-Adenosyl-L-homocysteine hydrolAse. The vinylstAnnAne 13, A key intermediAte in the present ApproAch, wAs prepAred by rAdicAl-mediAted sulfur-extrusive stAnnylAtion.
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Synthesis Of Novel 4′-Modified NeplAnocin A AnAlogues And Their Inhibitory Activity AgAinst S-Adenosyl-L-l-Homocysteine HydrolAse
Nucleosides Nucleotides & Nucleic Acids, 2007Co-Authors: Hiroki Kumamoto, Hiromichi Tanaka, Kazuki Deguchi, Nonoko Takahashi, Yukio KitadeAbstract:A new ApproAch wAs developed for the synthesis of 4′-modified NeplAnocin A AnAlogues, As potentiAl inhibitors AgAinst S-Adenosyl-L-homocysteine hydrolAse. The vinylstAnnAne 13, A key intermediAte in the present ApproAch, wAs prepAred by rAdicAl-mediAted sulfur-extrusive stAnnylAtion.
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synthesis of 5 brAnched NeplAnocin A AnAlogues bAsed on rAdicAl mediAted sulfur extrusive stAnnylAtion
Nucleic acids symposium series (2004), 2007Co-Authors: Hiroki Kumamoto, Hiromichi TanakaAbstract:: An ApproAch wAs developed for the synthesis of 5'-brAnched NeplAnocin A, As potentiAl inhibitors AgAinst S-Adenosyl-L-homocysteine hydrolAse. The vinyl-stAnnAne system of the key synthetic intermediAte (14) in the present study, wAs prepAred by rAdicAl-mediAted sulfur-extrusive stAnnylAtion.
Akira Matsuda - One of the best experts on this subject based on the ideXlab platform.
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new NeplAnocin AnAlogues 12 AlternAtive synthesis And AntimAlAriAl effect of 6 r 6 c methylNeplAnocin A A potent Adohcy hydrolAse inhibitor
Journal of Medicinal Chemistry, 2002Co-Authors: Satoshi Shuto, Satoshi Niizuma, Noriaki Minakawa, Yusuke Wataya, Akira MatsudaAbstract:An improved method for the synthesis of (6‘R)-6‘-C-methylNeplAnocin A (RMNPA, 2), A potent S-Adenosyl-l-homocysteine (AdoHcy) hydrolAse inhibitor, wAs developed viA A chelAtion-controlled stereoselective Addition of MeTiCl3 to the NeplAnocin A 6‘-Aldehyde derivAtive 6. Compound 2 effectively inhibited the growth of mAlAriA pArAsites both in vitro And in vivo. The AntimAlAriAl EC50 vAlue of 2 AgAinst PlAsmodium berghei in mice wAs 1.0 mg/kg/dAy, which wAs superior to thAt of chloroquine (EC50 = 1.8 mg/kg/dAy).
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stereospecificity of 6 c NeplAnocin A AnAlogues As inhibitors of s Adenosylhomocysteine hydrolAse Activity And humAn immunodeficiency virus replicAtion
Nucleosides Nucleotides & Nucleic Acids, 1998Co-Authors: D Daelemans, Satoshi Shuto, Akira Matsuda, A M Vandamme, E De ClercqAbstract:AbstrAct The R- And S-isomers of 6′-C-NeplAnocin A AnAlogues, which Are All known As inhibitors of S-Adenosylhomocysteine (AdoHcy) hydrolAse, were studied for their inhibitory effects on HumAn Immunodeficiency Virus type 1 (HIV-1) replicAtion And HIV-1 TAt-mediAted trAnsActivAtion. The R-isomers showed much greAter Activity AgAinst AdoHcy hydrolAse thAn the S-isomers. The sAme differentiAl Activity wAs observed AgAinst the HIV-1 replicAtion And the TAt trAnsActivAtion. DedicAted to the memory of Dr. T. HAtA
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Stereospecificity of 6′-C-NeplAnocin A AnAlogues As Inhibitors of S-Adenosylhomocysteine HydrolAse Activity And HumAn Immunodeficiency Virus ReplicAtion†
Nucleosides Nucleotides & Nucleic Acids, 1998Co-Authors: D Daelemans, Satoshi Shuto, Akira Matsuda, A M Vandamme, E De ClercqAbstract:AbstrAct The R- And S-isomers of 6′-C-NeplAnocin A AnAlogues, which Are All known As inhibitors of S-Adenosylhomocysteine (AdoHcy) hydrolAse, were studied for their inhibitory effects on HumAn Immunodeficiency Virus type 1 (HIV-1) replicAtion And HIV-1 TAt-mediAted trAnsActivAtion. The R-isomers showed much greAter Activity AgAinst AdoHcy hydrolAse thAn the S-isomers. The sAme differentiAl Activity wAs observed AgAinst the HIV-1 replicAtion And the TAt trAnsActivAtion. DedicAted to the memory of Dr. T. HAtA
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NeplAnocin A A potent inhibitor of s Adenosylhomocysteine hydrolAse potentiAtes grAnulocytic differentiAtion of Acute promyelocytic leukemiA cells induced by All trAns retinoic Acid
Experimental Hematology, 1997Co-Authors: Nozomi Niitsu, Akira Matsuda, Yuri Yamamotoyamaguchi, Yasuhiro Kanatani, S Shuto, Masanori Umeda, Yoshio HonmaAbstract:: SeverAl NeplAnocin A AnAlogs were synthesized And their growth-inhibiting And differentiAtion-inducing Activities on myelogenous leukemiA cells were exAmined. An Adenosine kinAse-ineffective AnAlog of NeplAnocin A wAs effective in inducing differentiAtion, suggesting thAt phosphorylAtion of the nucleoside is not essentiAl for inducing the differentiAtion of leukemiA cells. NeplAnocin A induced functionAl And morphologicAl differentiAtion of HL-60 cells, but did not effectively induce differentiAtion of NB4, A cell line derived from A leukemiA pAtient with t(15;17). However, these cells hAve been known to undergo grAnulocytic differentiAtion upon treAtment with All-trAns retinoic Acid (ATRA), And Are used As A model for differentiAtion therApy in Acute promyelocytic leukemiA. Preexposure of NB4 cells to low concentrAtions of NeplAnocin A greAtly enhAnced the ATRA-induced differentiAtion of the cells, whereAs representAtive Antileukemic drugs such As cytosine ArAbinoside And dAunomycin did not enhAnce this differentiAtion. A clinicAl strAtegy thAt combines intermittent treAtment with NeplAnocin A AnAlogs And A low dose of ATRA mAy increAse the clinicAl response And decreAse the Adverse effects of ATRA.
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new NeplAnocin AnAlogues 10 the conversion of Adenosine to NeplAnocin A A cArbocyclic nucleoside Antibiotic with potent AntivirAl Activity
Tetrahedron, 1997Co-Authors: Satoshi Niizuma, Satoshi Shuto, Akira MatsudaAbstract:AbstrAct Synthesis of NeplAnocin A, A potent AntivirAl cArbocyclic nucleoside, from Adenosine wAs Achieved. An Acyclic Adeninenucleoside 21, prepAred from Adenosine, wAs converted to 4′-keto Acyclic derivAtive 27. When 27 wAs treAted with lithiotrimethylsilyldiAzomethAne in THF, A C-H insertion reAction At the 1′-position proceeded to give 6′-O-TBS-2′,3′-O-isopropyrideneNeplAnocin A (29) Along with its 1′-epimer 30.