Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Water and methanol extracts of Rosa damascena exhibited moderate anti-HIV activity. The anti-viral activities of 9 compounds isolated from the methanol extract were compared. The tetrahydroxyflavanone (kaempferol, 1), was effective in reducing the maturation of infectious progeny virus apparently due to selective inhibition of the viral protease. On the other hand the pentahydroxyflavone (quercetin, 2) and two 3-substituted derivatives of kaempferol appeared to inhibit HIV-infection by preventing binding of gp120 to CD4. 2-Phenylethanol-O-(6-O-galloyl)-beta-D-glucopyranoside 8 interacted irreversibly with gp120 and neutralized virus infectivity. The differences in the modes of action of 1 and 8 can account for the apparent synergy of their anti-viral activities.
 ...
PMID:The anti-HIV activity and mechanisms of action of pure compounds isolated from Rosa damascena. 895 85

During the screening of the natural products for their ability to inhibit the binding of REV (regulation of virion expression) protein to [33P] labeled RRE (REV responsive element) RNA, two novel fungal metabolites, harziphilone and fleephilone, were isolated from the butanol-methanol (1:1) extract of the fermentation broth of Trichoderma harzianum by bioassay guided fractionation. The structures of these two new compounds were established by spectroscopic methods. Harziphilone and fleephilone showed inhibitory activity against the binding of REV-protein to RRE RNA with IC50 values of 2.0 microM and 7.6 microM, respectively. However both compounds did not protect CEM-SS cells from acute HIV infection at concentration levels up to 200 micrograms/ml using an XTT dye reduction assay. In addition, harziphilone demonstrated cytotoxicity at 38 microM against the murine tumor cell line M-109.
 ...
PMID:Harziphilone and fleephilone, two new HIV REV/RRE binding inhibitors produced by Trichoderma harzianum. 896 92

Mycoplasma penetrans isolated from clinical specimens of AIDS patients showed potent activity in tumor necrosis factor alpha (TNF alpha) production in THP-1, U937 and J22HL60 cell lines, and in the enhancement of HIV-1 replication in a dormantly-infected J22HL60 cell line as compared with the activities of other mycoplasmas. Both activities were found in the methanol layer but not in the chloroform layer of the membrane extracted by the Bligh-Dyer method. TNF alpha production was observed in the peritoneal macrophages from both lipopolysaccharide-responsive and -unresponsive mouse strains, and was not inhibited by polymyxin B. The induction of TNF alpha production and enhancement of HIV-1 replication were strongly inhibited by Concanavalin A-Sepharose. The inhibitory effect of Concanavalin A-Sepharose was partially prevented by sugars in the order methyl-alpha-D-mannopyranoside and methyl-alpha-D-glucopyranoside but not methyl-alpha-D-galactopyranoside. Anti-human TNF alpha antibody, however, did not reduce the activity of the methanol layer to enhance HIV-1 replication, suggesting that the methanol layer could enhance HIV-1 replication directly. These results suggest that the carbohydrate derived from M. penetrans might be responsible for the progression of HIV-1 infection.
 ...
PMID:Induction of tumor necrosis factor alpha (TNF alpha) and enhancement of HIV-1 replication in the J22HL60 cell line by Mycoplasma penetrans. 901 88

Nef is a 27 kDa myristylated phosphoprotein expressed early in infection by HIV. The N terminus of Nef is thought to play a vital role in the functions of this protein through its interactions with membrane structures. The solution structure of a 25-residue polypeptide corresponding to the N terminus of Nef (Nef1-25) has been investigated by 1H NMR spectroscopy. In aqueous solution at pH 4.8 and 281 K, this peptide underwent conformational averaging, with Pro13 existing in cis and trans conformations in nearly equal proportions. In methanol solution, however, the peptide adopted a well-defined alpha-helical structure from residues 6 to 22, with the N- and C-terminal regions having a less ordered structure. On the basis of a comparison of chemical shifts and NOEs, it appeared that this helical structure was maintained in aqueous trifluoroethanol (50% v/v) and to a lesser extent in a solution of SDS micelles. When the N-acetyl group was replaced by either an N-myristyl or a free ammonium group, there was little effect on the three-dimensional structure of the peptide in methanol; deamidation of the C terminus also had no effect on the structure in methanol. In water, the myristylated peptide aggregated. The similarity between the sequences of Nef1-25 and melittin is reflected in the similar structures of the two molecules, although the N-terminal helix of melittin is more defined. This similarity in structure raises the possibility that Nef1-25 not only interacts with membranes but also may be capable of disrupting them and causing cell lysis. This type of interaction could contribute at least in part to the killing of bystander cells in lymphoid tissues during HIV infection.
 ...
PMID:Solution structure of a polypeptide from the N terminus of the HIV protein Nef. 916 67

A methanol extract (PC) has been obtained from the Bulgarian medicinal plant Geranium sanguineum L. The antiinfective activity of the plant preparation was studied. The extract inhibited the reproduction of a range of viruses (influenza, herpes simplex, vaccinia, HIV-I) in cell cultures. Its antiinfluenza effect was most pronounced; PC reduced the infectivity of various influenza virus strains in vitro and protected mice in experimental influenza infection. The polyphenol extract inhibited the in vitro growth of Staphylococcus aureus and Candida albicans.
 ...
PMID:Antiinfective activity of a plant preparation from Geranium sanguineum L. 936 94

A series of 2-mercapto-4-R1-5-R2-N-[1-R4-5-(R3-amino)-1,2,4- triazol-3-yl] benzenesulphonamides [IIa-IIg, IIIa-IIId] was obtained by the reaction of N-(1,1-dioxo-6-R1-7-R2- 1,2,4-benzodithiazin-3-yl)-N'-R3-guanidines [Ia-Ig] with some hydrazines in methanol or pyridine medium. The mechanism for the reaction has been suggested. Preliminary screening data indicated that compounds [IIIa-IIIb] exhibit moderate anti HIV activity, and compounds [IIIa-IIId] anticancer activity. Some structure-activity relationships are also discussed.
 ...
PMID:2-Mercapto-N-(azolyl) benzenesulphonamides III. Synthesis of some new 2-mercapto-N-(5-amino-1,2,4-triazol-3-yl) benzenesulphonamide derivatives with potential anti-HIV or anticancer activity. 941 95

A simple, accurate and precise high-performance liquid chromatographic method has been developed for measurement of ritonavir concentrations in human plasma. Ritonavir was partitioned from the plasma using liquid-liquid extraction with a mixture of ethyl acetate and hexane at neutral pH, with an average recovery >80%. Following two sequential washings of the reconstituted sample with hexane, chromatographic separation was accomplished on a C18 analytical column with a mobile phase containing acetonitrile, methanol and 0.01 M tetramethylammonium perchlorate in 0.1% aqueous trifluoroacetic acid (40:5:55, v/v) with low wavelength UV detection at 205 nm. Standard curves were linear (r2>0.9998) over the concentration range 0.01-15 microg/ml with both inter- and intra-day coefficients of variation typically less than 5%. The stability of ritonavir in plasma was excellent, with no evidence of degradation after 5 days at room temperature or after 6 months in a freezer. Decontamination procedures for HIV-positive plasma samples showed 5.6 and 10.2% degradation following heating to 60 degrees C for 30 or 60 min, respectively.
 ...
PMID:Determination of ritonavir, a new HIV protease inhibitor, in biological samples using reversed-phase high-performance liquid chromatography. 951 64

NSC 615985 (UC 84) has demonstrated anti-HIV activity in the NCI-AIDS antiviral screen and was under consideration as an anti-AIDS drug. The compound was subsequently shown to be a non-nucleoside reverse transcriptase inhibitor (NNRTI). An HPLC method was developed for the analysis of NSC 615985 in mouse, dog and human plasma; and was used to study its stability in plasma and blood as well as its absorption and metabolism in mice. The method involved precipitation of plasma protein with three volumes of methanol followed by HPLC analysis of the supernatant. The HPLC analysis was carried out on a reversed-phase Nova-Pak C18 column with a mobile phase of KH2PO4 (0.01 M; pH 4.8)-acetonitrile (52:48, v/v) at a flow rate of 1 ml min-1 and quantification with a UV detector set at 259 nm. The lower limit of quantitation was 0.05 microgram ml-1 in 1 ml of dog or human plasma or 0.1 microgram ml-1 in 0.5 ml of mouse plasma. NSC 615985 was more stable in dog and human plasma than in mouse plasma, and was less stable in blood than in plasma of the three species investigated. Following bolus intravenous (i.v.) administration at 10 mg kg-1 to male CDF1 mice, NSC 615985 elimination followed biexponential kinetics with half-lives of 1 and 7 min, and was extensively metabolized. NSC 615985 was very poorly absorbed following oral (PO) administration as a suspension in water or in 20% lipid emulsion (Liposyn II). Following bolus subcutaneous (s.c.) administration of [14C]NSC 615985 at 10 mg kg-1, relatively low concentrations of the parent compound were observed in three of 36 mice. One metabolite was tentatively identified in plasma of both the i.v.- and s.c.-treated animals as the sulfoxide of the parent compound. No parent compound was detected in the urine of NSC 615985 dosed mice. At least seven metabolites were present in urine; one metabolite (constituting 8-14% of urinary radioactivity) was tentatively identified as the carboxylic acid resulting from the hydrolysis of the isopropyl group from the parent compound. In summary, NSC 615985 was poorly absorbed following oral administration and extensively metabolized and eliminated following i.v. or s.c. administration. This unfavorable pharmacokinetic profile of NSC 615985 as well as its pattern of activity against NNRTI-resistant strains of HIV-1 precluded its progression to clinical trial; however, other members of the general chemical class are currently being evaluated by the NCI.
 ...
PMID:Liquid chromatographic analysis in mouse, dog and human plasma; stability, absorption, metabolism and pharmacokinetics of the anti-HIV agent 2-chloro-5-(2-methyl-5,6-dihydro-1,4-oxathiin-3-yl carboxamido) isopropylbenzoate (NSC 615985, UC84). 960 23

2'-Beta-fluoro-2',3'-dideoxyadenosine (F-ddA, lodenosine) is an experimental anti-AIDS drug currently being evaluated in a Phase I clinical trial. A simple and specific HPLC method with UV detection, suitable for use in clinical studies, has been developed to determine both F-ddA and its deaminated catabolite, 2'-beta-fluoro-2',3'-dideoxyinosine (F-ddI) in human plasma. After inactivation of plasma HIV by 0.5% Triton X-100, the compounds of interest are isolated and concentrated using solid-phase extraction. Processed samples are separated by use of a pH 4.8 buffered methanol gradient on a reversed-phase phenyl column. The method has a linear range of 0.05-5 microg/ml (0.2-20 microM) and intra-assay precision is better than 8%. Analyte recovery is quantitative and plasma protein binding is minimal. In addition, drug and metabolite levels measured in Triton-treated human plasma remain stable for at least 5 months when samples are stored frozen without further treatment. Compound concentrations determined after samples are processed and then frozen for up to 1 month before analysis are also unchanged.
 ...
PMID:Determination of 2'-beta-fluoro-2',3'-dideoxyadenosine, an experimental anti-AIDS drug, in human plasma by high-performance liquid chromatography. 969 43

Recently, the authors were confronted with interference of stavudine and co-trimoxazole when analyzing the antiretroviral drug didanosine (ddI) in plasma of HIV-1-infected patients using reverse-phase high-performance liquid chromatography with ultraviolet detection. After increasing the percentage of methanol in the mobile phase from 4% to 8% vol/vol and after decreasing the pH of the mobile phase from 6.8 to 5.8, the authors were able to separate didanosine from stavudine and co-trimoxazole (both are frequently used drugs in combination with didanosine). Subsequently, the adapted bioanalytic methodology was validated, and validation results showed that this new methodology can be used for the quantitative determination of didanosine in human plasma. This observation makes clear that combination therapy for human immunodeficiency virus with multiple (often chemically related) drugs has the potential of unexpectedly complicating bioanalytic analyses because therapeutic strategies may change rapidly after publication of a bioanalytic methodology. Thus, it is evident that the investigation of interference of potentially coadministered drugs should be a standard procedure during the development of any bioanalytical methodology in any laboratory.
 ...
PMID:Co-trimoxazole and stavudine interference in a high-performance liquid chromatographic analysis for didanosine in human plasma. 985 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>