Abstract:
:The synthesis of the unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-d-glucopyranosyl nucleosides of 5-fluorouracil (6a), N(6)-benzoyl adenine (6b), uracil (6c), thymine (6d) and N(4)-benzoyl cytosine (6e), is described. Monoiodination of compounds 1a,b, followed by acetylation, catalytic hydrogenation and finally regioselective 2'-O-deacylation afforded the partially acetylated dideoxynucleoside analogues of 5-fluorouracil (5a) and N(6)-benzoyl adenine (5b), respectively. Direct oxidation of the free hydroxyl group at the 2'-position of 5a,b, with simultaneous elimination reaction of the beta-acetoxyl group, afforded the desired unsaturated 4,6-dideoxy-3-fluoro-2-keto-beta-D-glucopyranosyl derivatives 6a,b. Compounds 1c-e were used as starting materials for the synthesis of the dideoxy unsaturated carbonyl nucleosides of uracil (6c), thymine (6d) and N(4)-benzoyl cytosine (6e). Similarly a protection-selective deprotection sequence followed by oxidation of the free hydroxyl group at the 2'-position of the dideoxy benzoylated analogues 9c-e with simultaneous elimination reaction of the beta-benzoyl group, gave the desired nucleosides 6c-e. None of the compounds was inhibitory to a broad spectrum of DNA and RNA viruses at subtoxic concentrations. The 5-fluorouracil derivative 6a was more cytostatic (50% inhibitory concentration ranging between 0.2 and 12 microM) than the other compounds.
journal_name
Bioorg Chemjournal_title
Bioorganic chemistryauthors
Manta S,Tsoukala E,Tzioumaki N,Kiritsis C,Balzarini J,Komiotis Ddoi
10.1016/j.bioorg.2009.11.001subject
Has Abstractpub_date
2010-04-01 00:00:00pages
48-55issue
2eissn
0045-2068issn
1090-2120pii
S0045-2068(09)00091-1journal_volume
38pub_type
杂志文章abstract::Two series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 2,4-imidazolinedione/pyrazolone scaffold were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against HT-29, H460, A549, MKN-45, and U87MG cancer cell lines in vitro. The pharmacological data indicated that mo...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2014.07.011
更新日期:2014-12-01 00:00:00
abstract::Two new series of ethyl benzoate bearing pyrrolizine and indolizine moieties 8-11 were synthesized and evaluated for their anti-inflammatory and anticancer activities. Among these derivatives, compounds 9a, 10b and 11b displayed in vivo anti-inflammatory and analgesic activity comparable to ibuprofen. The acute ulcero...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103371
更新日期:2020-01-01 00:00:00
abstract::A series of tellurides was evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) carbonic anhydrase isoforms hCA I, II, IV, VII and IX, involved in a variety of diseases, including glaucoma, retinitis pigmentosa, epilepsy, arthritis and tumors. These compounds, which are the first tellurium...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2017.12.010
更新日期:2018-02-01 00:00:00
abstract::Implication of carbonic anhydrases (CAs) in many physiological functions made them attractive therapeutic targets. Herein, we report the synthesis of three series of benzenesulfonamide-based compounds (5a-e, 9a-e and 10a-e) as potential ligands to four of the human CA isoforms (hCA I, hCA II, hCA IX and hCA XII). All ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103635
更新日期:2020-03-01 00:00:00
abstract::Tumor hypoxia has been widely explored over the years as a diagnostic and therapeutic marker. Herein, we designed, optimized and synthesized a new multifunctional bioreductive linker (12) containing an alkynyl group (potential click chemistry fragment); the linker is based on 2-nitroimidazole which was expected to sim...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103975
更新日期:2020-08-01 00:00:00
abstract::The coenzyme function of ubiquinone was subject of extensive studies in mitochondria since more than 40 years. The catalytic activity of ubiquinone (UQ) in electron transfer and proton translocation in cooperation with mitochondrial dehydrogenases and cytochromes contributes essentially to the bioenergetic activity of...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1006/bioo.2000.1193
更新日期:2001-02-01 00:00:00
abstract::To understand the effect of counter ions (Na+) on the secondary conformation and functionality of the lysozyme, we have studied the interaction of lysozyme with counterion associated iron oxide nanoparticles (IONPs). The investigation was carried out at pH 7.4 and 9.0, with three different types of NPs, namely, bare I...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.09.020
更新日期:2019-02-01 00:00:00
abstract::The chemical investigation of the fruits of a mangrove Sonneratia apetala collected from the Beibu Gulf led to the isolation of four new compounds, sonneradons A-D (1-4), as well as 18 known compounds (5-22). The structures of the new compounds were elucidated based on extensive spectroscopic analysis, and the structu...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103813
更新日期:2020-06-01 00:00:00
abstract::Indoline framework is often perpended as a privileged heterocycle present in medicinally valuable compounds of natural and synthetic origin. This review article presents the rational approaches/strategies employed for the design of anticancer indolines along with the structure activity relationship and mechanistic ins...
journal_title:Bioorganic chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bioorg.2019.103436
更新日期:2020-01-01 00:00:00
abstract::In continuation of our previous work on the investigation of CDK9 inhibitors bearing indole moiety for the discovery of novel anticancer agents, novel methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold were designed, synthesized, and evaluated for the CDK9 i...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104064
更新日期:2020-09-01 00:00:00
abstract::A concise chemoenzymatic route toward enantiomerically enriched active pharmaceutical ingredients (API) - diprophylline and xanthinol nicotinate - is reported for the first time. The decisive step is an enantioselective lipase-mediated methanolysis of racemic chlorohydrin-synthon acetate, namely 1-chloro-3-(1,3-dimeth...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104448
更新日期:2021-01-01 00:00:00
abstract::In this paper, we present our investigation on ribonuclease A (RNase) modifications induced by 1,4-benzoquinone (PBQ), 2-methyl-1,4-benzoquinone (MBQ), and 2-chloro-1,4-benzoquinone (CBQ). The goal of the study was to evaluate quinone-induced protein modifications as well as substituent effects, utilizing several tech...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2015.02.004
更新日期:2015-04-01 00:00:00
abstract::Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/methyl/morpholinomethylpiperidinyl- methyl/pyrrolidinylmethyl-4H-pyran-4-one stru...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.102950
更新日期:2019-07-01 00:00:00
abstract::Glycyrrhetinic acid has been usually studied for their anti-tumor activities. However, the low bioavailability and poor aqueous solubility as well as limited intracellular accumulation have limited their utility. In this present study, a series of new glycyrrhetinic acid conjugates with a triphenylphosphonium cation (...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.12.036
更新日期:2019-04-01 00:00:00
abstract::A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell c...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2015.09.003
更新日期:2015-12-01 00:00:00
abstract::The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by a FAD-dependent UDP-Galp mutase. When the enzyme is reduced by sodium dithionite, its catalytic efficiency increases significantly. Since ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2003.08.002
更新日期:2003-12-01 00:00:00
abstract::Phosphite dehydrogenase catalyzes the NAD+-dependent oxidation of hydrogen phosphonate (common name phosphite) to phosphate in what amounts to a formal phosphoryl transfer reaction from hydride to hydroxide. This review places the enzyme in the context of phosphorus redox metabolism in nature and discusses the results...
journal_title:Bioorganic chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bioorg.2005.01.003
更新日期:2005-06-01 00:00:00
abstract::Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and H...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103054
更新日期:2019-09-01 00:00:00
abstract::Novel Mannich base analogues of pyrrolo[3,4-d]pyridazinone 7a,b-13a,b are designed and synthesized as potential anti-inflammatory agents. The title compounds are obtained via convenient one-pot synthesis with good yields. Their structures and properties are described by spectroscopic techniques and elemental analyses....
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104035
更新日期:2020-09-01 00:00:00
abstract::A series of polycyclic skeleton of truxene and triazatruxene analogs has been synthesized and evaluated for antitumor and DNA binding activities. The synthesized structures were confirmed by different spectroscopic techniques such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The antitumor screening was performed adopt...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.104323
更新日期:2020-11-01 00:00:00
abstract::In the present study, 7-subsituted coumarin derivatives were synthesized using various aromatic and heterocyclic amines, and evaluated in vivo for anti-inflammatory and analgesic activity, and for ulcerogenic risk. The most active compounds were evaluated in vitro for 5-lipoxygenase (5-LOX) inhibition. Docking study w...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2016.06.004
更新日期:2016-08-01 00:00:00
abstract::P-glycoprotein (P-gp) is one of the cell membrane pumps which mediate the efflux of molecules such as anticancer drugs to the extracellular matrix of tumor cells. P_gp is a member of the ATP-binding cassette (ABC) transporter family that is implicated in cancer multidrug resistance (MDR). Since MDR is a contributor to...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103156
更新日期:2019-10-01 00:00:00
abstract::Six new polyoxygenated seco-cyclohexenes, artahongkongenes A-F (1-6), together with six known analogues (7-12) were isolated from the stems and leaves of Artabotrys hongkongensis. Their structures were elucidated by extensive spectroscopic methods. All new compounds were evaluated for their cytotoxicities against five...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2017.12.011
更新日期:2018-02-01 00:00:00
abstract::We recently reported that esterification of 5'-AMP with N-acetyl amino acids proceeds with a preference for D-amino acids, and the D/L ratio in products declines as the hydrophobicity of the amino acid declines. Using one amino acid, Ac-Val, we now show that esterification of all four nucleotides proceeds with a pref...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/0045-2068(92)90019-y
更新日期:1992-01-01 00:00:00
abstract::Herein, we synthesized a series of twelve benzoxazole and benzothiazole derivatives incorporated with phthalimide core as anticancer agents. The most active compounds were 5a and 5g against HepG2 and MCF7 cell lines with IC50 = 0.011 and 0.006 μM, respectively. They evaluated against EGFR and HER2 enzymes. From cell c...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.102978
更新日期:2019-08-01 00:00:00
abstract::In an approach to develop potent cytotoxic compounds with targeted action, a systematic methodology was employed to design and initially synthesize parent compounds A1, A8, A13 and A14 followed by synthesis of further analogs of A1 (A2-A7) and A8 (A9-A12) with characterization by IR, NMR, mass and elemental techniques...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103539
更新日期:2020-01-01 00:00:00
abstract::Lambertellin (1) and ergosta-5,7,22-trien-3-ol (2) were isolated from the solid rice fermentation of the plant pathogenic fungus Pycnoporus sanguineus MUCL 51321. Their structures were elucidated using comprehensive spectroscopic methods. The isolated compounds were tested on lipopolysaccharide (LPS)-stimulated RAW 26...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2018.06.021
更新日期:2018-10-01 00:00:00
abstract::In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2019.103016
更新日期:2019-08-01 00:00:00
abstract::In addition to its catalytic domain, phosphoinsositide-dependent protein kinase-1 (PDK1) contains a C-terminal pleckstrin homology (PH) domain, which binds the membrane-bound phosphatidylinositol (3,4,5)-triphosphate [PI(3,4,5)P3] second messenger. Here, we report in vitro kinetic, phosphopeptide mapping, and oligomer...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2006.05.002
更新日期:2006-08-01 00:00:00
abstract::A series of furocoumarin-stilbene hybrids has been synthesized and evaluated in vitro for inhibitory effect against acetylcholinesterase (AChE), butyrylcholinestarase (BChE), β-secretase, cyclooxygenase-2 (COX-2), and lipoxygenase-5 (LOX-5) activities including free radical-scavenging properties. Among these hybrids, ...
journal_title:Bioorganic chemistry
pub_type: 杂志文章
doi:10.1016/j.bioorg.2020.103997
更新日期:2020-08-01 00:00:00