Anti-human immunodeficiency effects

Chen CH, Vazquez-Padua M et al (1991) Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. Mol Pharmacol 39(5) 625-628... 

Pontzer CH, Yamamoto JK, Bazer FW, Ott TL, Johnson HM. Potent anti-feline immunodificiency virus and anti-human immunodeficiency virus effect of interferon tau. J Immunol 1995 (in press). 

Schroder, H. C., Wenger, R., Gemer, H., Reuter, P., Kuchino, Y., Sladic, D., and Muller, W. E., Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan, Cancer Res., 49[8], 2069, 1989. 

Gallo JM, Swagler AR, Mehta M, Qian M. Pharmacokinetic evaluation of drug interactions with anti-human immunodeficiency virus drugs. VI. Effect of the calcium channel blocker nimodipine on zidovudine kinetics inmonkeys. JPharmacolExp Ther( 993) 264,315-20. 

SAR studies were carried out by de Bruyne et al. [92] on a series of dimeric procyanidins, considered as model compounds for antiviral therapies. On the whole, proanthocyanidins containing EC dimers exhibited more pronounced activity against herpes simplex virus (HSV) and human immunodeficiency virus (HIV), while the presence of ortho-trihydroxyl groups in the B-ring appeared to be essential in all proanthocyanidins exhibiting anti-HSV effects. Galloylation and polymerization reinforced the antiviral activities markedly. 

Up to this point, GIPF expressions have been formulated for only one type of biological activity - the inhibition of reverse transcriptase (RT), the enzyme that promotes the reverse transcription of genomic RNA into double-stranded DNA, a key step in the replication of the human immunodeficiency virus, HIV [82, 87]. Analytical representations were obtained for the anti-HIV potencies of three families of RT inhibitors the correlation coefficients are between 0.930 and 0.952. We are currently investigating the effects of applying the GIPF approach to certain portions of the molecules rather than their entireties. This might reveal the source of the activity, or alternatively, indicate it to be delocalized. 

The thiazoloimidazopyridine derivatives 451 were tested for their effect on human immunodeficiency virus (HIV)-induced cytopathogenicity in a human T4-lymphocyte cell line and showed a reproducible anti-HIV activity that caused a 50% or greater reduction of viral cytophatic effect <1994FA345>. Finally, imidazo[2,1 -/dthiazolone 489 was found to have an antitumor activity and proved to be effective against brain tumor cell lines <2002JHC1133>. 

A few nitrogen-substituted allenes themselves are known as biologically active compounds [154], For example, the 9-(4 -hydroxy-1, 2 -butadienyl)adenine (268a) was found to inhibit in vitro replication and cytopathic effects of human immunodeficiency viruses HIV-1 and HIV-2 [155], More recently, an increase in the anti-HIV activity in cell cultures using the adenallene phosphotriester derivative 268b was reported (Scheme 8.72) [156]. 

Low-energy ultrasound was employed to increase by up to 70% the production of shikonin (Fig. 4) in cell cultures of the medicinal herb Lithospermum erythrorhizon. Shikonin exhibits a variety of effects, which includes anti-inflammatory, antigonadotropic and human immunodeficiency virus type 1 (HIV-1) suppression activities. 

Furoannelated analogs of uracil acyclic nucleosides were prepared as compounds with potential as anti-HIV agents (HIV = human immunodeficiency virus). Hence, 6-benzyluracil 320 is converted to the precursor 321 first by hydroxymethylation, silylation in situ with bis(trimethylsilyl)acetamide (BSA), then by alkylation (Scheme 28) <2001S559>. Ring closure to 322 was effected by treatment with lead tetraacetate and calcium carbonate <2004AP148>. 

Soyasaponin I and II were studied in vitro against herpes simplex virus type I (HSV-1). Soyasaponin II was more potent than soyasaponin I in the reduction of HSV-1 production. Soyasaponin II was also found to inhibit the replication of human cytomegalovirus, influenza virus, and human immunodeficiency virus type 1. This activity was not due to the inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. When acyclovir and soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive antiviral effects were observed for this virus [160]. Astragaloside II afforded almost 100% protection of T-lymphocytes in vitro against the cytophatic effects of HIV infection. However, the EC50 of ca. 2.5 x 105 molar was difficult to achieve in vivo [98],... 

The history of combating the human immunodeficiency virus (HIV) can be viewed as a model of today s development of pharmaceuticals (Stone, 1995). Since the middle of the 1980s a total of 20 anti-AIDS pharmaceuticals based on 16 distinct chemical entities have been introduced into the market the first was AZT by Glaxo in 1987. A causal therapy, however, has not been developed yet. Most advantageous effects of today s actives are temporary because HIV is characterized by an extreme mutability and can cause resistance phenomena through rapid mutation within months or sometimes weeks against most approved preparations or those in clinical phases. The criterion for efficacy is the reduction of the number, or even total elimination, of viruses in the blood combined with an enhanced count of C D4-T-lymphocytes. 

Reverse transcription (which occurs in both prokaryotes and eukaryotes) is the synthesis of DNA from an RNA template. A class of RNA viruses, called retroviruses, are characterized by the presence of an RNA-dependent DNA polymerase (reverse transcriptase). The vims that causes AIDS, Human Immunodeficiency Virus (HIV), is a retro-vims. Because nuclear cell division doesn t use reverse transcriptase, the most effective anti-HIV drugs target reverse transcriptase, either its synthesis or its activity. Telomerase, discussed in the previous section, is a specialized reverse transcriptase enzyme. See Figure 12-5. 

PolyP with a chain length of more than four P residues inhibited human immunodeficiency virus type 1 (HIV-1) infection of cells in vitro at concentrations of > 300 /xM (in terms of Pi residues), whereas PolyP3 was ineffective (Lorenz et al., 1997b). This long-chain PolyP also inhibited HIV-1-induced syncytium formation. The anti-HIV effect of PolyPs may be due to the binding of the compounds to both the host cell surface and the virus, thereby inhibiting adsorption of the virus (Lorenz et al., 1997b). 

Another therapeutic application of polyhydroxylated alkaloids is as anti-viral agents. Inhibitors of processing a-glucosidases, such as castanospermine and DNJ, have been shown to decrease the infectivity of human immunodeficiency virus (HIV) in vitro at concentrations which are not cytotoxic to lymphocytes, whereas specific inhibitors of processing a-mannosidases (swainsonine and 1-deoxymannojirimycin) have no effect on Castanospermine and DNJ also reduce the infectivity of other retroviruses... 

A variety of mammalian cellular systems have been used as experimental models for documenting the in vitro effects of cannabinoids on immune responsiveness to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC had a protective effect against HSV infection in vitro. It was found that both HSV-1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.) in human cell monolayer cultures exposed before infection, at infection, or post infection to various concentrations of THC. In contrast, other studies indicate that THC compromises resistance to virus infection. It has been reported that THC inhibits macrophage extrinsic anti-viral activity (Cabral and Vasquez 1991 Cabral and Vdsquez 1992) whereby macrophages normally suppress virus replication in cells to which they attach (Morahan et al. 1980 Stohlman et al. 1982). Noe et al. (1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-2) cells infected with cell free human immunodeficiency virus (HIV-IMN). It was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly increased syncytia formation, a phenomenon that has been reported to serve as an indicator of HIV infection and cytopathicity. 

A gold complex auranofin has been developed for the treatment of rheumatoid arthritis. This is a typical linear two-coordinate complex of gold , with soft S and P donors to match the soft metal ion (Figure 9.4). The bulky ligands here promote compatibility in the bio-environment, and activity is influenced by the substituents on the RS and R3P ligands. Gold complexes have also been examined for antimicrobial, antimalarial and anti HIV (human immunodeficiency virus) activity. A copper(II) complex (Figure 9.4) is effective as a competitive inhibitor of HIV-1. 

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