Pub Date : 2019-08-05DOI: 10.1080/15257770.2019.1641206
D. Baraniak, P. Ruszkowski, Daniel Baranowski, G. Framski, J. Boryski
Abstract Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using “click” chemistry approach based on copper(I) catalyzed Huisgen azide–alkyne cycloaddition. It was performed between 3′- and 5′-azido-nucleosides as the azide components, and the 3′-O- and 5′-O-propargyl-nucleosides as the alkyne components. Based on analysis of the 3JHH, 3JH1′C2 and 3JH1′C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. All described nucleosides dimers analogs were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).
{"title":"Nucleoside dimers analogs containing floxuridine and thymidine with unnatural linker groups: synthesis and cancer line studies. Part III","authors":"D. Baraniak, P. Ruszkowski, Daniel Baranowski, G. Framski, J. Boryski","doi":"10.1080/15257770.2019.1641206","DOIUrl":"https://doi.org/10.1080/15257770.2019.1641206","url":null,"abstract":"Abstract Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using “click” chemistry approach based on copper(I) catalyzed Huisgen azide–alkyne cycloaddition. It was performed between 3′- and 5′-azido-nucleosides as the azide components, and the 3′-O- and 5′-O-propargyl-nucleosides as the alkyne components. Based on analysis of the 3JHH, 3JH1′C2 and 3JH1′C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. All described nucleosides dimers analogs were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"10 1","pages":"1005 - 980"},"PeriodicalIF":0.0,"publicationDate":"2019-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77733425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-02-01DOI: 10.1080/15257770.2016.1223306
C. S. Alexeev, G. Sivets, T. Safonova, S. Mikhailov
ABSTRACT Twenty five uridine analogues have been tested and compared with uridine with respect to their potency to bind to E. coli uridine phosphorylase. The kinetic constants of the phosphorolysis reaction of uridine derivatives modified at 2′-, 3′- and 5′-positions of the sugar moiety and 2-, 4-, 5- and 6-positions of the heterocyclic base were determined. The absence of the 2′- or 5′-hydroxyl group is not crucial for the successful binding and phosphorolysis. On the other hand, the absence of both the 2′- and 5′-hydroxyl groups leads to the loss of substrate binding to the enzyme. The same effect was observed when the 3′-hydroxyl group is absent, thus underlining the key role of this group. Our data shed some light on the mechanism of ribo- and 2′-deoxyribonucleoside discrimination by E. coli uridine phosphorylase and E. coli thymidine phosphorylase. A comparison of the kinetic results obtained in the present study with the available X-ray structures and analysis of hydrogen bonding in the enzyme-substrate complex demonstrates that uridine adopts an unusual high-syn conformation in the active site of uridine phosphorylase.
{"title":"Substrate specificity of E. coli uridine phosphorylase. Further evidences of high-syn conformation of the substrate in uridine phosphorolysis","authors":"C. S. Alexeev, G. Sivets, T. Safonova, S. Mikhailov","doi":"10.1080/15257770.2016.1223306","DOIUrl":"https://doi.org/10.1080/15257770.2016.1223306","url":null,"abstract":"ABSTRACT Twenty five uridine analogues have been tested and compared with uridine with respect to their potency to bind to E. coli uridine phosphorylase. The kinetic constants of the phosphorolysis reaction of uridine derivatives modified at 2′-, 3′- and 5′-positions of the sugar moiety and 2-, 4-, 5- and 6-positions of the heterocyclic base were determined. The absence of the 2′- or 5′-hydroxyl group is not crucial for the successful binding and phosphorolysis. On the other hand, the absence of both the 2′- and 5′-hydroxyl groups leads to the loss of substrate binding to the enzyme. The same effect was observed when the 3′-hydroxyl group is absent, thus underlining the key role of this group. Our data shed some light on the mechanism of ribo- and 2′-deoxyribonucleoside discrimination by E. coli uridine phosphorylase and E. coli thymidine phosphorylase. A comparison of the kinetic results obtained in the present study with the available X-ray structures and analysis of hydrogen bonding in the enzyme-substrate complex demonstrates that uridine adopts an unusual high-syn conformation in the active site of uridine phosphorylase.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"13 1","pages":"107 - 121"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79557198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-02-01DOI: 10.1080/15257770.2016.1226338
H. Dezhampanah, R. Firouzi, L. Hasani
ABSTRACT The interaction of nickel (II) phthalocyanine tetrasulfonic acid tetrasodium salt with bovine serum albumin (BSA) has been investigated by combination of fluorescence, UV-vis absorption, Fourier transform infrared (FT-IR), and circular dichorism (CD) spectroscopies as well as through molecular docking. Fluorescence quenching and absorption spectra were investigated as a mean for estimating the binding parameters. Analysis of fluorescence quenching data at different temperatures was performed in order to specify the thermodynamics parameters for interactions of phthalocyanine complex with BSA. According to experimental data it was suggested that phthalocyanine had a significant binding affinity to BSA and the process was entropy driven. Based on the results of molecular docking it was indicated that the main active binding site for this phthalocyanine complex is site I in subdomain IIA of BSA. The results provide useful information for understanding the binding mechanism of anticancer drug-albumin and gives insight into the biological activity and metabolism of the drug in blood.
{"title":"Intermolecular interaction of nickel (ii) phthalocyanine tetrasulfonic acid tetrasodium salt with bovine serum albumin: A multi-technique study","authors":"H. Dezhampanah, R. Firouzi, L. Hasani","doi":"10.1080/15257770.2016.1226338","DOIUrl":"https://doi.org/10.1080/15257770.2016.1226338","url":null,"abstract":"ABSTRACT The interaction of nickel (II) phthalocyanine tetrasulfonic acid tetrasodium salt with bovine serum albumin (BSA) has been investigated by combination of fluorescence, UV-vis absorption, Fourier transform infrared (FT-IR), and circular dichorism (CD) spectroscopies as well as through molecular docking. Fluorescence quenching and absorption spectra were investigated as a mean for estimating the binding parameters. Analysis of fluorescence quenching data at different temperatures was performed in order to specify the thermodynamics parameters for interactions of phthalocyanine complex with BSA. According to experimental data it was suggested that phthalocyanine had a significant binding affinity to BSA and the process was entropy driven. Based on the results of molecular docking it was indicated that the main active binding site for this phthalocyanine complex is site I in subdomain IIA of BSA. The results provide useful information for understanding the binding mechanism of anticancer drug-albumin and gives insight into the biological activity and metabolism of the drug in blood.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"24 1","pages":"122 - 138"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86488992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-02-01DOI: 10.1080/15257770.2016.1223305
N. Shahabadi, Farshad Shiri
ABSTRACT The interaction of copper(II)–ibuprofenato complex with calf thymus DNA (ct-DNA) has been explored following, UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, and circular dichroism spectroscopy. In spectrophotometric studies of ct-DNA it was found that [Cu(ibp)2]2 can form a complex with double-helical DNA. The association constant of [Cu(ibp)2]2 with DNA from UV-Vis study was found to be 6.19 × 104 L mol−1. The values of Kf from fluorescence measurement clearly underscore the high affinity of [Cu(ibp)2]2 to DNA. The experimental results showed that the conformational changes in DNA helix induced by [Cu(ibp)2]2 are the reason for the fluorescence quenching of the DNA-Hoechst system. In addition, the fluorescence emission spectra of intercalated methylene blue (MB) with increasing concentrations of [Cu(ibp)2]2 represented a significant increase of MB intensity as to release MB from MB-DNA system. The results of circular dichroism (CD) suggested that copper(II)–ibuprofenato complex can change the conformation of DNA. In addition, the results of viscosity measurements suggest that copper(II)–ibuprofenato complex may bind with non-classical intercalative mode. From spectroscopic and hydrodynamic studies, it has been found that [Cu(ibp)2]2 interacts with DNA by partial intercalation mode which contains intercalation and groove properties. GRAPHICAL ABSTRACT
{"title":"Multispectroscopic studies on the interaction of a copper(ii) complex of ibuprofen drug with calf thymus DNA","authors":"N. Shahabadi, Farshad Shiri","doi":"10.1080/15257770.2016.1223305","DOIUrl":"https://doi.org/10.1080/15257770.2016.1223305","url":null,"abstract":"ABSTRACT The interaction of copper(II)–ibuprofenato complex with calf thymus DNA (ct-DNA) has been explored following, UV-visible spectrophotometry, fluorescence measurement, dynamic viscosity measurements, and circular dichroism spectroscopy. In spectrophotometric studies of ct-DNA it was found that [Cu(ibp)2]2 can form a complex with double-helical DNA. The association constant of [Cu(ibp)2]2 with DNA from UV-Vis study was found to be 6.19 × 104 L mol−1. The values of Kf from fluorescence measurement clearly underscore the high affinity of [Cu(ibp)2]2 to DNA. The experimental results showed that the conformational changes in DNA helix induced by [Cu(ibp)2]2 are the reason for the fluorescence quenching of the DNA-Hoechst system. In addition, the fluorescence emission spectra of intercalated methylene blue (MB) with increasing concentrations of [Cu(ibp)2]2 represented a significant increase of MB intensity as to release MB from MB-DNA system. The results of circular dichroism (CD) suggested that copper(II)–ibuprofenato complex can change the conformation of DNA. In addition, the results of viscosity measurements suggest that copper(II)–ibuprofenato complex may bind with non-classical intercalative mode. From spectroscopic and hydrodynamic studies, it has been found that [Cu(ibp)2]2 interacts with DNA by partial intercalation mode which contains intercalation and groove properties. GRAPHICAL ABSTRACT","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"2 1","pages":"106 - 83"},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76217516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-19DOI: 10.1080/15257770.2016.1267361
K. Nguyen, K. Leydiker, Raymond Y. Wang, J. Abdenur, W. Nyhan
ABSTRACT We report a patient, an infant with a neurodevelopmental disorder manifesting intractable complex partial epilepsy, bull's eye maculopathy, microcephaly, bilateral cataracts, truncal hypotonia, and spasticity of all four extremities. Sequencing of genomic DNA revealed mutations in (a) exon 8 (Ox-2 antigen domain) of the amyloid precursor protein (APP) gene: c.1075C>T, p.Arg359* (b) exon 8 of the senataxin (SETX) gene: c.4738C>T, p.Arg1580Cys, and (c) exon 2 of the ceroid-lipofuscinosis, neuronal 8 (CLN8) gene: c.685C>G, p.Pro229Ala. Using a quantitative method for measurement of various APP-mRNA isoforms, we found that the APP-mRNA isoform of 624 bp with a deletion starting after 49 bp of the 5′ end of exon 3 followed by a complete deletion of exons 4–15, mutations in exon 1: c.22C>T, p.L18F, and exon 3: c.269A>G, p.Q90R encoding APP207 isoform was the most abundant one, and would appear to be responsible for the clinical manifestations. This is the first example that may underline the role of the epigenetic regulation in the expression of APP gene leading to a neurodevelopmental disorder resulting from a nonsense mutation in the Ox-2 antigen domain.
{"title":"A neurodevelopmental disorder with a nonsense mutation in the Ox-2 antigen domain of the amyloid precursor protein (APP) gene","authors":"K. Nguyen, K. Leydiker, Raymond Y. Wang, J. Abdenur, W. Nyhan","doi":"10.1080/15257770.2016.1267361","DOIUrl":"https://doi.org/10.1080/15257770.2016.1267361","url":null,"abstract":"ABSTRACT We report a patient, an infant with a neurodevelopmental disorder manifesting intractable complex partial epilepsy, bull's eye maculopathy, microcephaly, bilateral cataracts, truncal hypotonia, and spasticity of all four extremities. Sequencing of genomic DNA revealed mutations in (a) exon 8 (Ox-2 antigen domain) of the amyloid precursor protein (APP) gene: c.1075C>T, p.Arg359* (b) exon 8 of the senataxin (SETX) gene: c.4738C>T, p.Arg1580Cys, and (c) exon 2 of the ceroid-lipofuscinosis, neuronal 8 (CLN8) gene: c.685C>G, p.Pro229Ala. Using a quantitative method for measurement of various APP-mRNA isoforms, we found that the APP-mRNA isoform of 624 bp with a deletion starting after 49 bp of the 5′ end of exon 3 followed by a complete deletion of exons 4–15, mutations in exon 1: c.22C>T, p.L18F, and exon 3: c.269A>G, p.Q90R encoding APP207 isoform was the most abundant one, and would appear to be responsible for the clinical manifestations. This is the first example that may underline the role of the epigenetic regulation in the expression of APP gene leading to a neurodevelopmental disorder resulting from a nonsense mutation in the Ox-2 antigen domain.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"112 1","pages":"317 - 327"},"PeriodicalIF":0.0,"publicationDate":"2017-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80766285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-19DOI: 10.1080/15257770.2016.1257808
G. Elgemeie, A. Salah, N. S. Abbas, H. Hussein, Reham A. Mohamed
ABSTRACT A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N′-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N′-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.
{"title":"Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N-substituted amino and N-sulfonamide derivatives of pyrimidines","authors":"G. Elgemeie, A. Salah, N. S. Abbas, H. Hussein, Reham A. Mohamed","doi":"10.1080/15257770.2016.1257808","DOIUrl":"https://doi.org/10.1080/15257770.2016.1257808","url":null,"abstract":"ABSTRACT A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N′-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N′-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"57 1","pages":"213 - 223"},"PeriodicalIF":0.0,"publicationDate":"2017-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89690851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-19DOI: 10.1080/15257770.2016.1264590
J. Carter, Blair Weaver, M. Chiacchio, Amy R. Messersmith, W. Lynch, Brent D. Feske, G. Gumina
GRAPHICAL ABSTRACT ABSTRACT Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3′-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 μM concentration.
摘要:嘌呤霉素是一种肽基核苷，具有显著的抗生素和抗癌特性，但也具有不幸的肾毒性，这阻碍了它作为化疗药物的使用。由于嘌呤霉素酰胺水解为嘌呤霉素氨基核苷是导致肾毒性的第一个代谢步骤，我们设计了一个3 ' - c -肼类似物，其中嘌呤霉素酰胺羰基周围的氮和碳官能团被倒置。标题化合物由d -木糖经11步合成，不能代谢为肾毒性氨基核苷。在400 μM浓度下对表皮葡萄球菌和耐多药金黄色葡萄球菌的抑菌活性不显著。
{"title":"Synthesis, stereochemical characterization, and antimicrobial evaluation of a potentially nonnephrotoxic 3′-C-acethydrazide puromycin analog","authors":"J. Carter, Blair Weaver, M. Chiacchio, Amy R. Messersmith, W. Lynch, Brent D. Feske, G. Gumina","doi":"10.1080/15257770.2016.1264590","DOIUrl":"https://doi.org/10.1080/15257770.2016.1264590","url":null,"abstract":"GRAPHICAL ABSTRACT ABSTRACT Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3′-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside. Evaluation of the title compound on Staphylococcus epidermidis and multi-drug resistance Staphylococcus aureus did not show significant antimicrobial activity up to a 400 μM concentration.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"9 6 1","pages":"224 - 241"},"PeriodicalIF":0.0,"publicationDate":"2017-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79581819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-03DOI: 10.1080/15257770.2016.1250906
Robert P Van Ostrand, Casey Jacobsen, A. Delahunty, Carley Stringer, Ryan R. Noorbehesht, Haidi Ahmed, A. Awad
ABSTRACT Reported is an efficient synthesis of adenyl and uridyl 5′-tetrachlorophthalimido-5′-deoxyribonucleosides, and guanylyl 5′-azido-5′-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5′-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5′-hydroxyl with an azido group. The resulting compounds were converted to 5′-amino-5′-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2′,3′-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5′-tetrachlorophthalimido and 5′-azido demonstrated increased antibacterial effect.
报道了一种高效合成腺苷基、尿苷基5′-四氯眼酰基5′-脱氧核糖核苷和胍基5′-叠氮基5′-脱氧核糖核苷的方法，它们可用于固相合成磷酰胺和核糖核胍寡核苷酸。用四氯眼二胺组代替5′-羟基，通过Mitsunobu反应取代腺苷和尿苷。另一种方法是用叠氮基取代鸟苷的5′-羟基。所得化合物转化为5′-氨基-5′-脱氧核糖核苷，用于合成寡核苷酸。合成中间体对6种细菌菌株进行了抗菌试验。所有含有2 '，3 ' - o -异丙基保护基团的类似物对脑膜炎奈瑟菌均有抗菌活性，而含有5 ' -四氯眼二胺和5 ' -叠氮胺的类似物对脑膜炎奈瑟菌的抗菌作用更强。
{"title":"Synthesis and antibacterial activity of 5′-tetrachlorophthalimido and 5′-azido 5′-deoxyribonucleosides","authors":"Robert P Van Ostrand, Casey Jacobsen, A. Delahunty, Carley Stringer, Ryan R. Noorbehesht, Haidi Ahmed, A. Awad","doi":"10.1080/15257770.2016.1250906","DOIUrl":"https://doi.org/10.1080/15257770.2016.1250906","url":null,"abstract":"ABSTRACT Reported is an efficient synthesis of adenyl and uridyl 5′-tetrachlorophthalimido-5′-deoxyribonucleosides, and guanylyl 5′-azido-5′-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5′-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5′-hydroxyl with an azido group. The resulting compounds were converted to 5′-amino-5′-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2′,3′-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5′-tetrachlorophthalimido and 5′-azido demonstrated increased antibacterial effect.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"7 1","pages":"181 - 197"},"PeriodicalIF":0.0,"publicationDate":"2017-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87487822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-03DOI: 10.1080/15257770.2016.1231321
Katarzyna Kral, T. Bieg, A. Kudelko, A. Barabaś, A. Dąbrowska, I. Wandzik
ABSTRACT N-substituted isomeric hydrazones of uridyl aldehyde have been synthesized. The occurrence of the dominant E isomers with respect to the azomethine group was confirmed by means of NMR spectroscopy. Synthesized hydrazones feature an acetonide moiety as a protection of two hydroxyl groups on the ribose part. The attempt to remove the protecting group resulted in an azo-hydrazone tautomeric mixture. The described compounds may be valuable chiral ligands for metal chelation. Assessment of manganese(II) ion affinity to one selected hydrazone was performed.
{"title":"New N-substituted hydrazones, derivatives of uridyl aldehyde","authors":"Katarzyna Kral, T. Bieg, A. Kudelko, A. Barabaś, A. Dąbrowska, I. Wandzik","doi":"10.1080/15257770.2016.1231321","DOIUrl":"https://doi.org/10.1080/15257770.2016.1231321","url":null,"abstract":"ABSTRACT N-substituted isomeric hydrazones of uridyl aldehyde have been synthesized. The occurrence of the dominant E isomers with respect to the azomethine group was confirmed by means of NMR spectroscopy. Synthesized hydrazones feature an acetonide moiety as a protection of two hydroxyl groups on the ribose part. The attempt to remove the protecting group resulted in an azo-hydrazone tautomeric mixture. The described compounds may be valuable chiral ligands for metal chelation. Assessment of manganese(II) ion affinity to one selected hydrazone was performed.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"54 1","pages":"159 - 169"},"PeriodicalIF":0.0,"publicationDate":"2017-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75338564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-03DOI: 10.1080/15257770.2016.1231318
G. Elgemeie, A. Salah, N. S. Abbas, H. Hussein, Reham A. Mohamed
ABSTRACT The synthesis of a new category of novel cytosine 4-thioglycoside analogs has been first accomplished. The main step of this strategy is the synthesis of sodium pyrimidine-4-thiolate through the condensation of 2-cyano-N-arylacetamides with sodium cyanocarbonimidodithioate, followed by coupling with α-bromo-sugars to afford the corresponding cytosine 4-thioglycoside analogs. The free thioglycosides were also prepared. Subsequent studies on the application of this strategy for the preparation of other potent pyrimidine thioglycosides are reported.
摘要首次合成了一类新的胞嘧啶- 4-巯基糖苷类似物。该策略的主要步骤是通过2-氰- n -芳基乙酰胺与氰碳酰亚胺二硫代酸钠缩合合成嘧啶-4-硫代酸钠，然后与α-溴糖偶联得到相应的胞嘧啶-4-硫代糖苷类似物。并制备了游离巯基糖苷。随后对该策略在制备其他强效嘧啶硫代糖苷方面的应用进行了研究。
{"title":"Nucleic acid components and their analogs: Design and synthesis of novel cytosine thioglycoside analogs","authors":"G. Elgemeie, A. Salah, N. S. Abbas, H. Hussein, Reham A. Mohamed","doi":"10.1080/15257770.2016.1231318","DOIUrl":"https://doi.org/10.1080/15257770.2016.1231318","url":null,"abstract":"ABSTRACT The synthesis of a new category of novel cytosine 4-thioglycoside analogs has been first accomplished. The main step of this strategy is the synthesis of sodium pyrimidine-4-thiolate through the condensation of 2-cyano-N-arylacetamides with sodium cyanocarbonimidodithioate, followed by coupling with α-bromo-sugars to afford the corresponding cytosine 4-thioglycoside analogs. The free thioglycosides were also prepared. Subsequent studies on the application of this strategy for the preparation of other potent pyrimidine thioglycosides are reported.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"59 1","pages":"139 - 150"},"PeriodicalIF":0.0,"publicationDate":"2017-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85621893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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