A5029939214- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Pneumocystis jirovecii pneumonia detection and treatment
- DNA and Nucleic Acid Chemistry
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Biological Evaluation
- Peptidase Inhibition and Analysis
- Fluorine in Organic Chemistry
- Cytomegalovirus and herpesvirus research
- Chronic Lymphocytic Leukemia Research
- HIV/AIDS Research and Interventions
- Synthesis and biological activity
- Adenosine and Purinergic Signaling
- Research on Leishmaniasis Studies
- Organic and Inorganic Chemical Reactions
- Viral Infections and Immunology Research
- Glycosylation and Glycoproteins Research
- Cancer therapeutics and mechanisms
- Trypanosoma species research and implications
- Synthesis and Reactions of Organic Compounds
- Neuropeptides and Animal Physiology
Consejo Superior de Investigaciones Científicas
2010-2024
Instituto de Química Médica
2015-2024
Rega Institute for Medical Research
2000-2012
Stockholm University College of Music Education
2012
KU Leuven
1998-2009
Universidade da Coruña
2007
Universidad de Alcalá
1998-2006
Karolinska Institutet
1993-2006
University of Pittsburgh
2004-2006
Instituto de Ciencia y Tecnología de Polímeros
2006
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,2,3-Triazole-[2,5-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO) Analogs: Synthesis and Anti-HIV-1 ActivityRosa Alvarez, Sonsoles Velazquez, Ana San-Felix, Stefano Aquaro, Erik De Clercq, Carlo-Federico Perno, Anna Karlsson, Jan Balzarini, Maria Jose CamarasaCite this: J. Med. Chem. 1994, 37, 24, 4185–4194Publication Date (Print):November 1, 1994Publication History...
Several 5- N-alkyl and N,N-dialkylcarbamoyl substituted analogues of the anti-human immunodeficiency virus (HIV) type 1 lead compound[1-[2‘,5’-bis- O-( tert-butyldimethylsilyl)-β-D-ribofuranosyl]-5-( N,N-dimethylcarbamoyl)-1,2,3-triazole]-3‘-spiro-5“-(4”-amino-1“,2”-oxathiole-2“,2”-dioxide) have been prepared evaluated as inhibitors HIV-1 replication. A new regiospecific synthetic procedure is described. The compounds were by cycloaddition appropriate glycosylazide to...
A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-ribofuranose as the pentose were found to inhibit human immunodeficiency virus type 1 [HIV-1(IIIB)] replication at a concentration 0.06-0.8 microM but not cytotoxic 1000- 10,000-fold higher concentration. These derivatives also effective against various other HIV-1 strains, including those resistant 3'-azido-3'-deoxythymidine,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity [2', 5'-bis-O-(tert-butyldimethylsilyl)-.beta.-D-xylo- -ribofuranose]-3'-spiro-5''-[4''-amino-1'', 2''-oxathiole 2'', 2''-dioxide] (TSAO) pyrimidine nucleosidesMaria Jose Camarasa, Maria Jesus Perez-Perez, Ana San-Felix, Jan Balzarini, Erik De ClercqCite this: J. Med. Chem. 1992, 35, 15, 2721–2727Publication Date...
2',5'-Bis-O-(tert-buty1dimethylsilyl)-~-~-ribofur-anosy1]-3~-~pi~o-5''-(4''-amino-1'',2''-oxathio1e-2'', 2"-dioxide)thymine (TSAO-T) is a representative of novel class nucleoside analogues that are endowed with potent and specific activity against human immunodeficiency virus (HIV) type 1 targeted at the HIV-1 reverse transcriptase (RT).Inhibition RT by TSAO-T was reversible noncompetitive respect to dGTP as substrate poly(C).oligo(dG) template/primer.In contrast nonnucleoside derivatives...
Chikungunya virus (CHIKV) is a re-emerging Alphavirus that transmitted to humans by Aedes mosquitoes. Currently, there are still no drugs or vaccines available for the treatment prevention of this disease. Although traditionally restricted Africa and Asia, adaptation albopictus, mosquito species with an almost worldwide distribution, has contributed geographical spread in past decade. Here, we report on new family compounds named [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones inhibit CHIKV...
Human immunodeficiency virus type 1 (HIV-1)-infected CEM cells were treated by the HIV-1-specific inhibitors bis-heteroarylpiperazine (BHAP), 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1 H)-on e (TIBO) R82913, nevirapine, and N3-methylthymine derivative of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO-m3T), as single agents or in combination, at escalating concentrations. When used...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTSAO analogs. Stereospecific synthesis and anti-HIV-1 activity of 1-[2',5'-bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)pyrimidine pyrimidine-modified nucleosidesMaria Jesus Perez-Perez, Ana San-Felix, Jan Balzarini, Erik De Clercq, Maria Jose CamarasaCite this: J. Med. Chem. 1992, 35, 16, 2988–2995Publication Date (Print):August 1, 1992Publication History Published online1 May...
tert-Butyldimethylsilyl-spiroaminooxathioledioxide (TSAO) compounds have an embedded thymidine-analogue backbone; however, TSAO invoke non-nucleoside RT inhibitor (NNRTI) resistance mutations. Our crystal structure of RT:7 (TSAO-T) complex shows that 7 binds inside the NNRTI-binding pocket, assuming a "dragon" shape, and interacts extensively with almost all pocket residues. The also explains structure-activity relationships data for compounds. binding causes hyper-expansion significant...
We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series chalcones, whose prototype compound is (E)-3-(3''-amino-4''-methoxyphenyl)-1-(5'-methoxy-3',4'-methylendioxyphenyl)-2-methylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to colchicine site tubulin therefore prevent curved-to-straight structural transition tubulin, which required for microtubule formation. Accordingly, TUB091 inhibited...
Chikungunya virus (CHIKV) is a re-emerging alphavirus transmitted to humans by Aedes mosquitoes. Since 2005, CHIKV has been spreading worldwide resulting in epidemics Africa, the Indian Ocean islands, Asia and more recently Americas. thus considered as global health concern. There no specific vaccine or drug available for treatment of this incapacitating viral infection. We previously identified 3-aryl-[1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones selective inhibitors replication proposed...
Microtubule-targeting agents that bind at the colchicine-site of tubulin are particular interest in antitumoral therapy due to their dual mechanism action as antimitotics and vascular disrupting agents. Cyclohexanediones derivatives have been described a new family colchicine-domain binders with an association constant similar colchicine. Here, high-resolution structures complex cyclohexanediones TUB015 TUB075 were solved by X-ray crystallography. A detailed analysis tubulin-TUB075...
The influenza virus glycoprotein hemagglutinin (HA) participates in critical steps of the attachment viral particles to host cell membrane receptor and fusion. Due its crucial involvement initial phases A infections, HA emerges as a promising target search novel drug-like candidates. Given pivotal role early stages intense drug discovery efforts have been undertaken past decades. Drug studies mainly rely on preventing recognition sialic acid units by binding site globular head (GH) domain,...
Abstract Determination of the three-dimensional structure human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) has indicated a totally different folding for 51-kDa subunit (p51) than 66-kDa (p66). The polymerase catalytic site is located on p66 subunit. Moreover, HIV-1-specific RT inhibitors, also designated as non-nucleoside inhibitors (NNRTIs), select amino acid mutations that afford resistance to these compounds and are clustered in palm domain HIV-1 This pocket vicinity...
To progress the anti-varicella-zoster-virus (VZV) aryl bicyclic nucleoside analogues (BCNAs) to point of Phase 1 clinical trial for herpes zoster.A new chromatography-free synthetic access lead anti-VZV BCNAs is reported. The activity Cf1743 was evaluated in monolayer cell cultures and organotypic epithelial raft primary human keratinocytes. Oral dosing rodents preliminary pharmacokinetics assessment made, followed by an exploration alternative formulations preparation pro-drugs. We also...
Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to necrosis. Our approach for identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) using ROCS program as VS tool and query colchicine TN-16, which both bind α,β-tubulin dimer. One hits identified, TN-16 query, been explored by synthesis its structural analogues, 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione...
A series of acyclic phosphonate derivatives thymine has been synthesized and tested as multisubstrate analogue inhibitors Escherichia coli thymidine phosphorylase. The compounds include 1-(phosphonoalkyl)thymines with six to nine methylenes (1−4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) its butyl 2,3-cis-dihydroxybutyl (6 7, 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) also analogues (9 10); 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine (11)....
7‐Deazaxanthine (7DX) was identified as a novel inhibitor of thymidine (dThd) phosphorylase (TPase). It inhibited the TPase reaction in concentration‐dependent manner. At 1 mM, it almost completely prevented TPase‐catalysed hydrolysis dThd to thymine. The 50% inhibitory concentration (IC 50 ) 7DX 40 μM presence 100 natural substrate dThd. is also endowed with marked effect on angiogenesis. significantly prevents neovascularisation chicken chorioallantoic membrane during development. first...
A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem 2013) has been designed synthesized by introduction lactam between amino acid side chains that are separated one helical turn (i, i+4). All these compounds were tested in vitro as both dimerization enzyme inhibitors Leishmania infantum trypanothione reductase (Li-TryR). Three peptide derivatives (3, 4 6) inhibited oxidoreductase activity Li-TryR...