Anti-HIV treatment

BMY 40900 Videx ) is a synthetic reverse transcriptase INHIBITOR, active as an ANTIVIRAL and used in anti-hiv treatment. It is mainly administered to patients who are intolerant to. or have not benefited from, zidovudine, didehydroproline oxytocin ((t -Pro joxytocin) is an analogue of oxytocin and an agonist at oxytocin receptors (i.e. an (OT) VASOPRESSIN RECEPTOR AGONIST) with greater OXYTOCIC activity than oxytocin. 

Stavudine [inn, usan] (d4T Zerit ) is a synthetic thymidine nucleoside group reverse trascriptase inhibitor ANTIVIRAL AGENT, clinically used orally in anti-hiv treatment. StC 1400 fludrocortisone. 

An impressive example of the application of structure-based methods was the design of a inhibitor of the HIV protease by a group of scientists at DuPont Merck [Lam et al. 1994 This enzyme is crucial to the replication of the HIV virus, and inhibitors have bee shown to have therapeutic value as components of anti-AIDS treatment regimes. The star1 ing point for their work was a series of X-ray crystal structures of the enzyme with number of inhibitors boimd. Their objective was to discover potent, novel leads whid were orally available. Many of the previously reported inhibitors of this enzyme possessei substantial peptide character, and so were biologically unstable, poorly absorbed am rapidly metabolised. 

Mitochondria-associated toxicities, such as pancreatitis, are frequently demonstrated in HlV/HCV-coinfected individuals, and may significantly influence treatment options (de Mendoza and Soriano 2005). Yet, no cell culture or animal models have been developed to predict nucleoside-induced pancreatitis. Nevertheless, an association of HCV replication and mitochondrial DNA depletion in primary human lymphocytes obtained from HIV/HCV-coinfected individuals under concomitant administration of HCV and HIV medications was demonstrated by de Mendoza and coworkers (de Mendoza et al. 2007). They claimed that the use of HCV medication together with certain antiretroviral agents seemed to enhance mitochondrial damage due to a synergistic deleterious interaction between the anti-HCV and anti-HIV drugs. In contrast, an improvement in mitochondrial content with effective... 

There are currently six major antiretroviral drug families (Table 5). Nucleoside reverse transcriptase inhibitors (NRTI) are nucleoside analogs (discussed in more detail in chapter by De Clercq and Neyts, this volume) and were the first approved antiretroviral agents. They include drugs such as AZT, didanosine (ddl), stavudine (d4T), abacavir (ABC), and lamivudine (3TC), the latest used at doses of 300 mg daily as anti-HIV agent (lOOmg/day is the dosing approved for treatment of HBV... 

The best example of using this knowledge in drug discovery is the identification of Prostratin. While working in Samoa to identify plants with potential chemotherapeutic properties, Dr. Paul Cox documented the use of Homalanthus nutans for the treatment of hepatitis [16]. Surprisingly, when extracts of this plant were incidentally examined for anti-HIV properties, the extract appeared effective for treatment of HIV [17]. Eventually, this compound was shown to be effective at activating the latently infected T-cell pool [18]. Importantly, this population of cells is a principal reason for HIV persistence [19]. 

In addition to the three anti-HIV agents [AZT (zidovudine), DDI (dida-nosine) and DDC (zalcitabine)] that have been formally approved by the U.S. Food and Drug Administration for the treatment of HIV infections, several other 2, 3 -dideoxynucleoside (ddN) analogues (Fig. 5), including 3 -fluoro-2, 3 -didcoxy-5-chlorouridine (FddClUrd) and 2, 3 -didehydro-... 

De Clercq E. Anti-HIV agents interfering with the initial stages of the HIV replicative cycle. In Morrow WJW, Haigwood NL, eds. HIV Molecular Organization, Pathogenicity and Treatment. Amsterdam Elsevier Science Publishers, 1993 267-292. 

Arylmethyl-9-hydroxypyrazino[l,2-f]pyrimidine-l,8-dione derivatives have been claimed as anti-HIV agents <2005W02005/016927, 2005W02005/087766> 6,8-dioxo-pyrazino[l,2-f]pyrimidine-3-carboxamides 164 (Y = NH) <2004W02004/014354> and their saturated analogues <2004USP2004/034009> have been claimed as matrix metalloproteinase MMP-13 enzyme inhibitors, useful in the treatment of rheumatoid arthritis. 

Ribozymes are a class of metallo-enzymes based on RNA rather than proteins. They have potential in clinical medicine, for example, as potential anti-HIV agents (568, 569) and as possible new tools for the treatment of cancer (570). The active structures of ribozymes contain domains of stacked helices which pack together through tertiary contacts. Divalent metal ions such as Mg(II), Zn(II), and Mn(II) can tune the reactivity and shape the structures of ribozymes (571). Manganese(II) and Mg(II) have similar hexacoordinate ionic radii (0.86 and 0.97 A, respectively) (572) and octahedral geometry ( )Ka of hydrates Ca(II), 12.7 Mg(II), 11.4 Mn(II), 10.7 Zn2+, 9.6) (571). There are several potential oxygen donors on the ribose sugar moiety. 

The rapid identification of anti-HIV compounds in the laboratory following the isolation of the causative virus in 1983 and their subsequent use in treatment was not unexpected. Three decades of previous work has established a scientific basis for the evaluation of antiviral compounds. However, no antiviral yet discovered can cause total blockade of a virus replicating in a cell. The combination of properties of HIV, including latency and antigenic and biochemical variation, is unusual, and the virus represents a daunting challenge for chemotherapy. 

Erythropoietin is a protein produced mainly in the cortex of the kidney. Erythropoietin binds to a receptor on the surface of erythroid precursor cells. It stimulates erythropoiesis and is primarily indicated for the treatment of anemia in patients with chronic renal failure. Other indications are the management of anemia in cancer patients and in HIV positive subjects treated with anti-HIV regimens. 

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