当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and activity of nucleoside-based antiprotozoan compounds.

Synthesis and activity of nucleoside-based antiprotozoan compounds.

Abstract：

:Parasitic protozoa employ a salvage pathway to synthesize purines and generate essential active nucleotides, whereas mammals are capable of their de novo biosynthesis. This difference provides opportunity for the design of potential new antiprotozoan compounds. A series of 47 adenosine analogues was prepared with modifications at the 2-, 6- and 5'-positions, based on the hypothesis that such compounds would serve as substrates for protozoan nucleoside salvage enzymes, while remaining refractory in mammalian cells. The nucleosides were designed to produce toxic metabolites upon cleavage to the corresponding purine base by the parasite. Three 7-deazaguanosine derivatives were prepared with similar objectives. All of these compounds were tested in vitro against T. brucei (African sleeping sickness), T. cruzi (Chagas' disease), L. donovani (leishmaniasis) and P. falciparum (malaria). In order to determine the therapeutic selectivity indices (SI) of the antiprotozoan nucleosides, their cytotoxicities toward a rat myoblast cell line were also determined. One adenosine derivative proved highly effective against P. falciparum (IC50=110nM and SI=1010, while a modified guanosine displayed potent activities against L. donovani (IC50=60nM, SI=2720) and T. brucei (IC50=130nM, SI=1250), as well as moderate activity against T. cruzi (IC50=3.4µM, SI=48). These results provide proof of concept for the nucleoside-based antiprotozoan strategy, as well as potential lead compounds for further optimization and validation.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Tran HA,Zheng Z,Wen X,Manivannan S,Pastor A,Kaiser M,Brun R,Snyder FF,Back TG

doi

10.1016/j.bmc.2017.02.016

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

2091-2104

issue

7

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(16)31409-2

journal_volume

25

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • An evaluation of central penetration from a peripherally administered oxytocin receptor selective antagonist in nonhuman primates.

    abstract：:The physiology of the oxytocin receptor has increasingly become a focus of scientific investigation due to its connection with social behavior and psychiatric disorders with impairments in social funciton. Experimental utilization of small molecule and peptide antagonists for the oxytocin receptor has played a role in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.10.035

    authors： Smith AL,Walum H,Connor-Stroud F,Freeman SM,Inoue K,Parr LA,Goodman MM,Young LJ

    更新日期：2017-01-01 00:00:00

  • Construction of a chemically and conformationally self-replicating system of amyloid-like fibrils.

    abstract：:The amyloid-like fibril is considered to be a macromolecular self-assemblage with a highly-ordered quaternary structure, in which numerous beta-stranded polypeptide chains align regularly. Therefore, this kind of fibril has the potential to be engineered into proteinaceous materials, although conformational alteration...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.11.022

    authors： Takahashi Y,Mihara H

    更新日期：2004-02-15 00:00:00

  • Design and synthesis of an all-in-one 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group for photo-affinity labeling.

    abstract：:A novel radioisotope-free photo-affinity probe containing the 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group was designed and synthesized. This very compact functionality is envisaged to allow photochemically-induced coupling of a compound to its target followed by click reaction coupling with an azido-...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.06.048

    authors： Kumar NS,Young RN

    更新日期：2009-08-01 00:00:00

  • In-situ side-chain peptide cyclization as a breaker strategy against the amyloid aggregating peptide.

    abstract：:Accumulation and deposition of misfolded amyloid β (Aβ) peptide outside the nerve cells are one of the major causes of Alzheimer's disease (AD). To date, one of the promising therapeutic strategies for AD is to block the early steps associated with the aggregation of Aβ peptide. We have developed synthetic breaker pep...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2021.116017

    authors： Ghosh N,Kundu LM

    更新日期：2021-01-16 00:00:00

  • Design and synthesis of novel benzimidazole derivatives as inhibitors of hepatitis B virus.

    abstract：:A series of novel benzimidazole derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in the HepG2.2.15 cell line. The preliminary SAR was discussed. Compound 12a, with IC50<0.41 microM and SI>81.2, was the most promising compound and selected as the benchmark comp...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.076

    authors： Luo Y,Yao JP,Yang L,Feng CL,Tang W,Wang GF,Zuo JP,Lu W

    更新日期：2010-07-15 00:00:00

  • Structure-activity relationships and key structural feature of pyridyloxybenzene-acylsulfonamides as new, potent, and selective peroxisome proliferator-activated receptor (PPAR) γ Agonists.

    abstract：:In our search for a novel class of non-TZD, non-carboxylic acid peroxisome proliferator-activated receptor (PPAR) γ agonists, we explored alternative lipophilic templates to replace benzylpyrazole core of the previously reported agonist 1. Introduction of a pentylsulfonamide group into arylpropionic acids derived from...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.03.036

    authors： Rikimaru K,Wakabayashi T,Abe H,Tawaraishi T,Imoto H,Yonemori J,Hirose H,Murase K,Matsuo T,Matsumoto M,Nomura C,Tsuge H,Arimura N,Kawakami K,Sakamoto J,Funami M,Mol CD,Snell GP,Bragstad KA,Sang BC,Dougan DR,Tanak

    更新日期：2012-05-15 00:00:00

  • Expanding the repertoire of small molecule transcriptional activation domains.

    abstract：:Molecules that can reconstitute the function of transcriptional activators hold enormous potential as therapeutic agents and as mechanistic probes. Previously we described an isoxazolidine bearing functional groups similar to natural transcriptional activators that up-regulates transcription 80-fold at 1 microM in cel...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.02.045

    authors： Casey RJ,Desaulniers JP,Hojfeldt JW,Mapp AK

    更新日期：2009-02-01 00:00:00

  • Axial chirality and affinity at the GABA(A) receptor of pyrimido[1,2-a][1,4]benzodiazepines and related compounds.

    abstract：:The pyrimido[1,2-a][1,4]benzodiazepines (1a-c) and the 8-membered analogues (diazocines 2a and 2b) were separated into their atropisomers with HPLC on a chiral column. High stereochemical stability was observed in the atropisomer of the 8-membered derivatives (2a and 2b), and the 1,4-benzodiazepine (1c) with 2'-chloro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.09.037

    authors： Lee S,Kamide T,Tabata H,Takahashi H,Shiro M,Natsugari H

    更新日期：2008-11-01 00:00:00

  • Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage.

    abstract：:An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a-e and 4a-j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, rat liver homogenate lipid ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.03.032

    authors： Gong J,Huang K,Wang F,Yang L,Feng Y,Li H,Li X,Zeng S,Wu X,Stöckigt J,Zhao Y,Qu J

    更新日期：2009-05-01 00:00:00

  • Identification and characterization of novel sirtuin inhibitor scaffolds.

    abstract：:The sirtuin proteins are broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes including DNA recombination and repair, transcriptional silencing, longevity, apoptosis, axonal protection, insulin signaling, and fat mobilization. Because of these associations, the identifica...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.07.073

    authors： Sanders BD,Jackson B,Brent M,Taylor AM,Dang W,Berger SL,Schreiber SL,Howitz K,Marmorstein R

    更新日期：2009-10-01 00:00:00

  • Visual observation of G-quadruplex DNA with the label-free fluorescent probe silole with aggregation-induced emission.

    abstract：:AIE molecule silole 1 could be used to detect G-quadruplex formation using an exonuclease I hydrolysis assay. This visual observation of G-quadruplexes has been successfully used in investigating multiple G-quadruplexes, including the one-stranded telomeric, c-myc, c-kit, VEGF G-quadruplexes, and a d(G(4)T(4)G(4)) int...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.09.040

    authors： Huang J,Wang M,Zhou Y,Weng X,Shuai L,Zhou X,Zhang D

    更新日期：2009-11-15 00:00:00

  • New, stronger nucleophiles for nucleic acid-templated chemistry: Synthesis and application in fluorescence detection of cellular RNA.

    abstract：:Nucleic acid-templated chemistry is a promising strategy for imaging genetic sequences in living cells. Here we describe the synthesis of two new nucleophiles for use in templated nucleophilic displacements with DNA probes. The nucleophilic groups are phosphorodithioate and phosphorotrithioate; we report on synthetic ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.04.051

    authors： Miller GP,Silverman AP,Kool ET

    更新日期：2008-01-01 00:00:00

  • Design, synthesis and biological activity of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists.

    abstract：:The free fatty acid receptor 1 (FFA1) is a novel antidiabetic target for the treatment of type 2 diabetes based on particular mechanism in amplifying glucose-stimulated insulin secretion. We have previously identified a series of phenoxyacetic acid derivatives. Herein, we describe the further chemical modification of ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.10.011

    authors： Li Z,Wang X,Xu X,Yang J,Xia W,Zhou X,Huang W,Qian H

    更新日期：2015-11-15 00:00:00

  • Novel steroidal vinyl fluorides as inhibitors of steroid C17(20) lyase.

    abstract：:20-fluoro-17(20)-pregnenolone derivatives were designed as enol mimics of pregnenolone. All of the targeted, novel fluoroolefins were potent inhibitors of C17(20) lyase. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00354-6

    authors： Burkhart JP,Weintraub PM,Gates CA,Resvick RJ,Vaz RJ,Friedrich D,Angelastro MR,Bey P,Peet NP

    更新日期：2002-04-01 00:00:00

  • Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity.

    abstract：:Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (±)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (±)-stepholidine, were synthesized and evaluated for affinity at dopamine and σ receptors in order to evaluate effects on...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.03.037

    authors： Gadhiya S,Madapa S,Kurtzman T,Alberts IL,Ramsey S,Pillarsetty NK,Kalidindi T,Harding WW

    更新日期：2016-05-01 00:00:00

  • Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action.

    abstract：:New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.01.010

    authors： Raimondi MV,Listro R,Cusimano MG,La Franca M,Faddetta T,Gallo G,Schillaci D,Collina S,Leonchiks A,Barone G

    更新日期：2019-03-01 00:00:00

  • Synthesis and biological evaluation of novel phthalazinone derivatives as topically active phosphodiesterase 4 inhibitors.

    abstract：:Inhibitors of phosphodiesterase 4 (PDE4) are an important class of anti-inflammatory drug that act by inhibiting the production of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). We have synthesized and evaluated a series of 2-substituted phthalazinone derivatives as PDE4 inhibitors. Stru...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.08.014

    authors： Kagayama K,Morimoto T,Nagata S,Katoh F,Zhang X,Inoue N,Hashino A,Kageyama K,Shikaura J,Niwa T

    更新日期：2009-10-01 00:00:00

  • The design of a novel near-infrared fluorescent HDAC inhibitor and image of tumor cells.

    abstract：:Histone deacetylases (HDACs) have been found to be biomarkers of cancers and the corresponding inhibitors have attracted much attention these years. Herein we reported a near-infrared fluorescent HDAC inhibitor based on vorinostat (SAHA) and a NIR fluorophore. This newly designed inhibitor showed similar inhibitory ac...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115639

    authors： Huang Y,Ru HB,Bao B,Yu JH,Li J,Zang Y,Lu W

    更新日期：2020-09-01 00:00:00

  • Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action.

    abstract：:Novel benzimidazole derivatives were synthesized and their pharmacological activities were examined. These compounds showed a good suppressive action on histamine release from rat peritoneal mast cells produced by antigen-antibody reaction, an antagonistic action on guinea pig ileum contraction caused by histamine, an...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00291-6

    authors： Nakano H,Inoue T,Kawasaki N,Miyataka H,Matsumoto H,Taguchi T,Inagaki N,Nagai H,Satoh T

    更新日期：2000-02-01 00:00:00

  • Aza-THIP and related analogues of THIP as GABA C antagonists.

    abstract：:The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K(i)=25 microM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xe...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.09.016

    authors： Krehan D,Frølund B,Ebert B,Nielsen B,Krogsgaard-Larsen P,Johnston GA,Chebib M

    更新日期：2003-11-17 00:00:00

  • Synthesis of oxytocin derivatives lipidated via a carbonate or carbamate linkage as a long-acting therapeutic agent for social impairment-like behaviors.

    abstract：:In the course of our studies of hydrophobic oxytocin (OT) analogues, we newly synthesized lipidated OT (LOT-4a-c and LOT-5a-c), in which a long alkyl chain (C14-C16) is conjugated via a carbonate or carbamate linkage at the Tyr-2 phenolic hydroxy group and a palmitoyl group at the terminal amino group of Cys-1. These ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.06.018

    authors： Cherepanov SM,Miura R,Shabalova AA,Ichinose W,Yokoyama S,Fukuda H,Watanabe M,Higashida H,Shuto S

    更新日期：2019-08-01 00:00:00

  • Thiopyrano[2,3-e]indol-2-ones: angelicin heteroanalogues with potent photoantiproliferative activity.

    abstract：:A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.10.002

    authors： Barraja P,Diana P,Montalbano A,Carbone A,Cirrincione G,Viola G,Salvador A,Vedaldi D,Dall'acqua F

    更新日期：2008-11-15 00:00:00

  • Novel 3,6-bis(imidazolidine)acridines as effective photosensitizers for photodynamic therapy.

    abstract：:The photoeffect of new proflavine derivatives with DNA-binding and antitumour activities, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs), was studied to evaluate them as potential photosensitizers for photodynamic antitumor therapy. EPR measurements showed that superoxide radical ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.07.013

    authors： Cižeková L,Grolmusová A,Ipóthová Z,Barbieriková Z,Brezová V,Hunáková L,Imrich J,Janovec L,Dovinová I,Paulíková H

    更新日期：2014-09-01 00:00:00

  • Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related furazan derivatives.

    abstract：:Synthesis and pharmacological characterisation of a series of compounds in which the oxime substructure present in imoproxifan was constrained in the pentatomic NO-donor furoxan ring, as well as their structurally related furazan analogues devoid of NO-donating properties, are described. The whole series of products d...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.05.004

    authors： Tosco P,Bertinaria M,Di Stilo A,Cena C,Sorba G,Fruttero R,Gasco A

    更新日期：2005-08-01 00:00:00

  • Peptide T-araC conjugates: solid-phase synthesis and biological activity of N4-(acylpeptidyl)-araC.

    abstract：:Due to the capability of peptidyl derivatives of araC to behave as prodrugs of this antimetabolite, and because of the well known biological properties of peptide T and its analogues (in particular that of targeting CD4+ cells), new peptide T-araC conjugates were prepared and tested in vitro for antiproliferative acti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00317-x

    authors： Manfredini S,Marastoni-M,Tomatis R,Durini E,Spisani S,Pani A,Marceddu T,Musiu C,Marongiu ME,La Colla P

    更新日期：2000-03-01 00:00:00

  • Development and evaluation of a 68Ga labeled pamoic acid derivative for in vivo visualization of necrosis using positron emission tomography.

    abstract：:In this study, we labeled N,N'-bis(diethylenetriamine pentaacetic acid)-pamoic acid bis-hydrazide (bis-DTPA-PA) with the generator produced PET radionuclide gallium-68 and evaluated 68Ga-bis-DTPA-PA as a potential tracer for in vivo visualization of necrosis by positron emission tomography (PET). Radiolabeling was ach...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.050

    authors： Prinsen K,Li J,Vanbilloen H,Vermaelen P,Devos E,Mortelmans L,Bormans G,Ni Y,Verbruggen A

    更新日期：2010-07-15 00:00:00

  • Design, synthesis, and subtype selectivity of 3,6-disubstituted β-carbolines at Bz/GABA(A)ergic receptors. SAR and studies directed toward agents for treatment of alcohol abuse.

    abstract：:A series of 3,6-disubstituted β-carbolines was synthesized and evaluated for their in vitro affinities at α(x)β(3)γ(2) GABA(A)/benzodiazepine receptor subtypes by radioligand binding assays in search of α(1) subtype selective ligands to treat alcohol abuse. Analogues of β-carboline-3-carboxylate-t-butyl ester (βCCt, 1...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.08.049

    authors： Yin W,Majumder S,Clayton T,Petrou S,VanLinn ML,Namjoshi OA,Ma C,Cromer BA,Roth BL,Platt DM,Cook JM

    更新日期：2010-11-01 00:00:00

  • Dolichylpyrophosphate oligosaccharides: large-scale isolation and evaluation as oligosaccharyltransferase substrates.

    abstract：:Oligosaccharyltransferase (OST) catalyzes the transfer of a branched oligosaccharide from a dolichylpyrophosphate oligosaccharide (Dol-PP-OS) to the asparagine of a nascent polypeptide chain in vivo and peptide substrates in vitro. Here we report the isolation and purification of Dol-PP-OS from bovine pancreas and thy...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(98)00268-5

    authors： Gibbs BS,Coward JK

    更新日期：1999-03-01 00:00:00

  • Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery.

    abstract：:Twenty-four asymmetric divalent head group cholesterol-based cationic lipids were designed and synthesized by parallel solid phase chemistry. These asymmetric head groups composed of amino functionality together with trimethylamino, di(2-hydroxyethyl)amino or guanidinyl groups. Spacers between cationic heads and linke...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.10.057

    authors： Radchatawedchakoon W,Watanapokasin R,Krajarng A,Yingyongnarongkul BE

    更新日期：2010-01-01 00:00:00

  • Structure-activity relationships of truncated adenosine derivatives as highly potent and selective human A3 adenosine receptor antagonists.

    abstract：:On the basis of potent and selective binding affinity of truncated 4'-thioadenosine derivatives at the human A(3) adenosine receptor (AR), their bioisosteric 4'-oxo derivatives were designed and synthesized from commercially available 2,3-O-isopropylidene-D-erythrono lactone. The derivatives tested in AR binding assay...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.03.034

    authors： Pal S,Choi WJ,Choe SA,Heller CL,Gao ZG,Chinn M,Jacobson KA,Hou X,Lee SK,Kim HO,Jeong LS

    更新日期：2009-05-15 00:00:00