A5013898612- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Mosquito-borne diseases and control
- Pneumocystis jirovecii pneumonia detection and treatment
- Protein Tyrosine Phosphatases
- Click Chemistry and Applications
- Chronic Lymphocytic Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- DNA and Nucleic Acid Chemistry
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- Adenosine and Purinergic Signaling
- Fluorine in Organic Chemistry
- Fibroblast Growth Factor Research
- Cytomegalovirus and herpesvirus research
- Cancer therapeutics and mechanisms
- HIV/AIDS Research and Interventions
- Viral Infections and Immunology Research
- Organophosphorus compounds synthesis
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
Instituto de Química Médica
2015-2025
Center for Research in Molecular Medicine and Chronic Diseases
2025
Universidade de Santiago de Compostela
2025
Vall d'Hebron Hospital Universitari
2024
Consejo Superior de Investigaciones Científicas
2006-2018
Universidad Autónoma de Madrid
2018
Madrid Institute for Advanced Studies
2018
IMDEA Food
2018
Centro Nacional de Biotecnología
2018
Cleveland Clinic Lerner College of Medicine
2014
The unique characteristics of the tumor vasculature offer possibility to selectively target growth and vascularization using tubulin-destabilizing agents. Evidence accumulated with combretastatin A-4 (CA-4) its prodrug CA-4P support therapeutic value compounds sharing this mechanism action. However, chemical instability poor solubility CA-4 demand alternative that are able surmount these limitations. This Perspective illustrates different classes behave similar CA-4, analyzes their binding...
The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and lack of vaccines or therapeutics. We discovered novel class small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected these carried P34S substitution non-structural protein 1 (nsP1), main enzyme involved alphavirus RNA...
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...
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...
We recently reported that a newly discovered class of nucleoside analogues--[2',5'-bis-O-(tert-butyldimethylsilyl)- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D - pentofuranosyl derivatives pyrimidines and purines (designated TSAO)--are highly specific inhibitors human immunodeficiency virus type 1 (HIV-1) targeted at the nonsubstrate binding site HIV-1 reverse transcriptase (RT). now find strains selected for resistance against three different TSAO retain sensitivity...
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...
Rationale : Platelets contain abundant thymidine phosphorylase (TYMP), which is highly expressed in diseases with high risk of thrombosis, such as atherosclerosis and type II diabetes mellitus. Objective To test the hypothesis that TYMP participates platelet signaling promotes thrombosis. Methods Results By using a ferric chloride (FeCl 3 )–induced carotid artery injury thrombosis model, we found time to blood flow cessation was significantly prolonged Tymp −/− +/− mice compared wild-type...
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...
Enteroviruses (family of the Picornaviridae) cover a large group medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects viral life cycle, in particular morphogenesis, are yet poorly understood. We report discovery TP219 as novel inhibitor replication several enteroviruses, including coxsackievirus and poliovirus. show that binds directly glutathione (GSH), thereby rapidly depleting intracellular GSH...