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Titolo:
New developments in anti-HIV chemotherapy
Autore:
De Clercq, E;
Indirizzi:
Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 s, B-3000 Louvain, Belgium
Titolo Testata:
CURRENT MEDICINAL CHEMISTRY
fascicolo: 13, volume: 8, anno: 2001,
pagine: 1543 - 1572
SICI:
0929-8673(200111)8:13<1543:NDIAC>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; CHEMOKINE RECEPTOR CXCR4; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SMALL-MOLECULE INHIBITOR; STRUCTURE-BASED DESIGN; METHYLENECYCLOPROPANE NUCLEOSIDE ANALOGS; TETRAD-FORMING OLIGONUCLEOTIDES; CHRONICALLY INFECTED-CELLS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
228
Recensione:
Indirizzi per estratti:
Indirizzo: De Clercq, E Katholieke Univ Leuven, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium Katholieke Univ Leuven Minderbroedersstr 10 Louvain Belgium B-3000
Citazione:
E. De Clercq, "New developments in anti-HIV chemotherapy", CURR MED CH, 8(13), 2001, pp. 1543-1572

Abstract

Virtually all the compounds that are currently used, or under advanced clinical trial, for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e., zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir (ABC), emtricitabine [(-)FTC], tenofovir (PMPA) disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs); i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and 442); and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir. In addition to the reverse transcriptase and protease step, various other events in the HIV replicative cycle are potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polyoxometalates, zintevir, negativelycharged albumins, cosalane analogues); (Li) viral entry, through blockade of the viral coreceptors CXCR4 and CCR5 [bicyclams (i.e. AMD3100), polyphemusins (T22), TAK-779, MIP-1 alpha LD78 beta isoform]; (iii) virus-cell fusion, through binding to the viral glycoprotein gp41 [T-20 (DP-178), T-1249 (DP-107), siamycins, betulinic acid derivatives]; (Lv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA) and NCp7 peptide mimics); (v) proviral DNA integration, through integrase inhibitors such as L-chicoric acid and diketo acids (i.e. L-731,988); (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (fluoroquinolone K-12, Streptomyces product EM2487, temacrazine, CGP64222). Also, in recent years new NRTIs, NNRTIs and Pis have been developed that possess respectively improved metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides of d4T), or increased activity against NNRTI-resistant HIV strains [second generation NNRTIs, such as capravirine and the novel quinoxaline, quinazolinone, phenylethylthiazolylthiourea (PETT) and emivirine (MKC-442) analogues], or, as in the case of Pls, a different, non-peptidic scaffold [i.e. cyclic urea (DMP 450), 4-hydroxy-2-pyrone (tipranavir)]. Given the multitude of molecular targets with which anti-HIV agents can interact, oneshould be cautious in extrapolating from cell-free enzymatic assays to themode of action of these agents in intact cells. A number of compounds (i.e. zintevir and L-chicoric acid, on the one hand; and CGP64222 on the other hand) have recently been found to interact with virus-cell binding and viral entry in contrast to their proposed modes of action targeted at the integrase and transactivation process, respectively.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 08:05:09