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

Methanol and water extracts of the root of Epinetrum villosum (Exell) Troupin (Menispermaceae) were found to exhibit antimicrobial and antiplasmodial activities. Investigation of the active methanol fraction led to the isolation of four bisbenzylisoquinoline alkaloids, i.e., cycleanine, cycleanine N-oxide, isochondodendrine and cocsoline. Structures were established by spectroscopic methods. Cocsoline displayed antibacterial and antifungal activities (MIC values of 1000-15.62 and 31.25 microg/ml, respectively). Isochondodendrine was found to have the most potent antiplasmodial activity (IC50 = 0.10 microg/ml), whereas the IC50 on HCT-116 human colon carcinoma cells was 17.5 microg/ml (selectivity index 175). Cycleanine acted against HIV-2 (EC50=1.83 microg/ml) but was at least 10-fold less active against HIV-1. Cycleanine N-oxide showed no activity towards all tested microorganisms.
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PMID:Biologically active bisbenzylisoquinoline alkaloids from the root bark of Epinetrum villosum. 1599 41

We developed a simple HPLC method for the simultaneous quantitative determination of seven HIV protease inhibitors: amprenavir (APV), atazanavir (ATV), indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and a nonnucleoside reverse transcription inhibitor, efavirenz (EFV). This method involves a rapid liquid-liquid drug extraction from plasma, the use of an isocratic elution on a reversed-phase C18 column, and an ultraviolet detection at a single wavelength (205 nm). The mobile phase consisted of 39% 50 mM phosphate buffer (pH 5.9), 22% methanol and 39% acetonitrile. Forty-eight samples could be measured in one day since the runtime of one sample is 30 min. The assay has been validated over a concentration range of 0.05 to 12.20 microg/ml for APV, 0.09 to 12.05 microg/ml for ATV, 0.05 to 12.01 microg/ml for IDV, 0.12 to 12.36 microg/ml for LPV, 0.18 to 12.20 microg/ml for NFV, 0.12 to 12.33 microg/ml for RTV, 0.12 to 12.06 microg/ml for SQV, and 0.05 to 12.17 microg/ml for EFV. Calibration curves were linear in the described concentration ranges. The average accuracy ranged from 97.2 to 106.8%. Both the interday and intraday coefficients of variation for all drugs tested were less than 8.5%. This method provides a simple, accurate, and precise method for the therapeutic drug monitoring of the seven protease inhibitors and EFV in clinical routine use.
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PMID:Conventional HPLC method used for simultaneous determination of the seven HIV protease inhibitors and nonnucleoside reverse transcription inhibitor efavirenz in human plasma. 1599 15

For the first time approved antiretroviral drugs, i.e. protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI), were quantified in dried blood spots (DBS) from HIV/AIDS patient whole blood samples as the basis for therapeutic drug monitoring (TDM) by a robust simultaneous liquid chromatography/tandem mass spectrometry (LC/MS/MS) method. This study included seven PI (amprenavir, nelfinavir, indinavir, lopinavir, saquinavir, ritonavir, atazanavir) and two NNRTI (nevirapine, efavirenz). LC/MS/MS coupling was realized using a Phenomenex Synergy Max RP LC column (150 x 2 mm, 4 micro) in combination with a tandem mass spectrometer (API 2000, Applied Biosystems/MDS Sciex Concord) operating in positive and negative multiple reaction monitoring (MRM) mode with reserpine as internal standard. DBS samples were punched out and extracted with 50:50 MeOH/0.2 M ZnSO4 (v/v) as extraction reagent. The method performance data for the drugs in DBS like limits of detection (LOD, 8-70 ng/mL), lower limits of quantification (LLOQ, 41-102 ng/mL), linearity (R2, 0.9981-0.9999), linear concentration ranges (41-10.000 ng/mL), accuracies (92-113%), recoveries (62-94%), and ion suppression were investigated and are comparable to data obtained from human plasma, which is the current standard matrix for TDM of PI and NNRTI. In this case, off-line plasma sample preparation was performed by means of simple protein precipitation with 80:20 methanol/0.2 M ZnSO4 (v/v) as precipitation reagent. Significant correlations between real patient plasma and DBS were obtained for samples containing lopinavir, atazanavir, ritonavir, saquinavir, and efavirenz. DBS preparation as sampling alternative is well suited and practicable for TDM minimizing the high infection risk of HIV/AIDS samples and may facilitate sample mailing.
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PMID:Quantification of antiretroviral drugs in dried blood spot samples by means of liquid chromatography/tandem mass spectrometry. 1619 30

Searching for anti-HIV-1 protease (PR) inhibitors of Thai medicinal plants led to the isolation of a new cyclohexenyl chalcone named panduratin C (1) and chalcone derivatives (2-6) from the methanol extract of Boesenbergia pandurata rhizomes. The known compounds were identified to be panduratin A (2), hydroxypanduratin A (3), helichrysetin (4), 2',4',6'-trihydroxyhydrochalcone (5), and uvangoletin (6). The structures of all compounds were elucidated on the basis of chemical and spectroscopic methods. It was found that 3 possessed the most potent anti-HIV-1 PR activity with an IC50 value of 5.6 microM, followed by 2 (IC50 = 18.7 microM), whereas other compounds exhibited only mild activity. Structure-activity relationships of these compounds on anti-HIV-1 PR activity are summarized as follows: (1) hydroxyl moiety at position 4 conferred higher activity than methoxyl group; (2) prenylation of dihydrochalcone was essential for activity; (3) hydroxylation at position 4''' reduced activity; and (4) introduction of double bond at C1' and C6' of chalcone gave higher activity. As regards active constituents contained in B. pandurata rhizomes, hydroxypanduratin A (3) and panduratin A (2) are active principles against HIV-1 PR.
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PMID:Anti-HIV-1 protease activity of compounds from Boesenbergia pandurata. 1626 98

In vitro anti-HIV activity of various extracts prepared from the stem bark of Combretum molle (R. Br. Ex. G. Don.) Engl & Diels (Combretaceae), a plant widely used in Ethiopian traditional medicine for the treatment of liver diseases, malaria and tuberculosis has been assessed against human imnmuunodeficiencvy virus type 1 (HIV-1) and type 2 (HIV-2). The total extract was prepared by percolation with 80% methanol whilst the petroleum ether, chloroform, acetone and 100% methanol fractions were obtained by successive hot extraction using Soxhlet apparatus. Selective inhibition of viral growth was assessed by the simultaneous determination of the in vitro cytotoxicity of each of the extracts against MT-4 cells. Results obtained in this study indicate that the acetone fraction possessed the highest selective inhibition of HIV-1 replicatuon. Phytochemical investigation of the acetone fraction resulted in the isolation of two tannins and two oleanane-type pentacyclic triterpene glycosides. One of the tannins was identified as puncalagin (an ellagitannin), whilst the structure of the other (CM-A) has not yet been fully elucidated. The saponins that were characterized as arjunglucoside (also called 4-epi-sericoside) and sericoside did not inhibit replication of either HIV-1 or HIV-2. On the other hand, both punicalgin and CM-A displayed selective inhibition of HIV-1 replication with selectrvitv indices (ratio of 50% cytotoxic concentration to 50% effective antiviral concentration) of 16 and 25, respectivelvy and afforded cell protection of viral induced cytopathic effect of 100% when compared with control samples. Neither of the tannins exhibited a selective inhibition to HIV-2 replication at nontoxic doses.
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PMID:Anti-HIV activity against immunodeficiency virus type 1 (HIV-I) and type II (HIV-II) of compounds isolated from the stem bark of Combretum molle. 1637 May 25

Therapeutic drug monitoring (TDM) is pivotal to improve the management of HIV infection. Here, a HPLC-UV method has been developed to quantify simultaneously seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir; PIs), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine; NRTIs), and two non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine; NNRTIs) in human plasma. The volume of the plasma sample was 600 microL. This method involved automated solid-phase extraction with Oasis HLB Cartridge 1 cc (divinylbenzene and N-vinylpyrrolidone) and evaporation in a water bath under nitrogen stream. The extracted samples were reconstituted with 100 microL methanol. Twenty microliters of these samples were injected into a HPLC-UV system, the analytes were eluted on an analytical C(18) Symmetry column (250 mm x 4.6mm I.D.) with a particle size of 5 microm. The mobile phase (0.01 M KH(2)PO(4) and acetonitrile) was delivered at 1.0 mL/min with linear gradient elution. The total run time for a single analysis was 35 min, the anti-HIV drugs were detected by UV at 240 and 260 nm. The calibration curves were linear up to 10 microg/mL. The absolute recovery ranged between 88 and 120%. The in vitro stability of anti-HIV drugs (0.005-10 microg/mL) in plasma has been studied at 24.0 degrees C. On these bases, a two to four analyte method has been tailored to the individual needs of the HIV-infected patient. The HPLC-UV method here reported has been validated and is currently applied to monitor PIs, NRTIs, and NNRTIs in plasma of HIV-infected patients. It allows to monitor the largest number of anti-HIV drugs simultaneously, appearing useful in a routine laboratory, and represents an essential step to elucidate the utility of a formal therapeutic drug monitoring for the optimal follow-up of HIV-infected patients.
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PMID:Simultaneous determination of 16 anti-HIV drugs in human plasma by high-performance liquid chromatography. 1640 32

The synthesis of a new series of abacavir prodrugs involving N2-substitution with various substituted benzaldehyde and ketone derivatives is described. The in vitro anti-HIV activities indicated that compound (3-(2-(4-methylaminobenzylideneamino)-6-(cyclopropylamino)-9H-purin-9-yl)cyclopentyl)methanol (3) was found to be most potent compound with EC50 of 0.05 microM and CC50 of >100 microM with selectivity index of >2000. Compound 3 was found to be 32 times more potent than the parent drug (EC50 of 1.6 microM). At pH 7.4, 37 degrees C, the hydrolytic t1/2 ranged between 120 and 240 min.
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PMID:Abacavir prodrugs: microwave-assisted synthesis and their evaluation of anti-HIV activities. 1645 6

The donor-acceptor interaction between a tertiary amine and an aldehyde, first observed among a select class of alkaloids, was deliberately established in a peptidomimetic (1a-c) to mimic features of the two principal transition states of peptide hydrolysis. Compounds 1a-c show preferential adoption in methanol and water of a 'folded' conformation displaying the interaction. Proportions of the folded form in MeOH range from 45% to 70% and can reach 84% in buffer. Significantly, three tendencies for the folded/unfolded equilibrium are observed: increasing solubility and polarity of the medium and decreasing temperature results in a higher extent of folding. In the absence of any parameter set available for this weak bond, no modeling studies were conducted to aid in the design of 1a-c. The successful straightforward synthesis of 1 and its folding and inhibition results with HIV-1 peptidase using FRET technology encourage studies to further pre-organize candidate molecules and to screen the structure space by modeling and parallel combinatorial chemistry.
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PMID:An unusual functional group interaction and its potential to reproduce steric and electrostatic features of the transition states of peptidolysis. 1646

The antiretroviral therapeutic drug monitoring is becoming increased in clinical care to determine the best dosage regimen adapted to each patient. Here, the determination of the anti-HIV drugs lamivudine, lopinavir, and ritonavir concentration in the plasma of HIV-infected patients by MALDI-TOF/TOF is reported. The volume of the plasma sample was 600 microL. Plasma samples were extracted by solid-phase (divinylbenzene and N-vinylpyrrolidone) and evaporated in a water bath under a nitrogen stream. The extracted samples were reconstituted with methanol (100 microL), mixed (1:1) with a saturated matrix solution (4-hydroxybenzoic acid in 50% acetonitrile-0.1% trifluoracetic acid), and spotted onto the MALDI-TOF/TOF sample target plate. The lamivudine, lopinavir and ritonavir concentration was determined by standard additions analysis. Regression of standard additions was linear over the anti-HIV drug concentration ranges explored (lamivudine, 0.010-1.0 pmol/microL; lopinavir and ritonavir, 0.0025-0.50 pmol/microL). Moreover, emtricitabine (i.e., the fluorinated analog of lamivudine) was used as the internal standard to determine the lamivudine concentration. The calibration curve was linear on the emtricitabine concentration ranging between 0.050 and 5.0 pmol/microL. The absolute recovery ranged between 80 and 110%. Values of the lamivudine, lopinavir and ritonavir concentration determined by MALDI-TOF/TOF are in excellent agreement with those obtained by HPLC-UV and HPLC-MS/MS. MALDI-TOF/TOF experiments allowed also the detection of the ritonavir metabolite R5. Zidovudine was undetectable by MALDI-TOF/TOF analysis because also the minimal laser intensity may induce the anti-HIV drug photolysis. The MALDI-TOF/TOF technique is useful to determine very low concentrations of anti-HIV drugs (0.0025-0.010 pmol/microL).
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PMID:Determination of anti-HIV drug concentration in human plasma by MALDI-TOF/TOF. 1650 54

In the present paper we describe the cloning and extracellular expression of the HIV-1 Nef (negative factor) protein utilizing the yeast Pichia pastoris, as well as the successful use of a low-temperature fed-batch strategy for decreasing end-product degradation by proteases. The nef gene in a pPICZalphaA vector was integrated into the genome of three different P. pastoris strains, namely X-33, GS115 and KM71H. On the basis of its efficient growth and production characteristics the wild-type strain (X-33) was found to be the best choice. The decreased end-product degradation at low temperatures was not due to lower amounts of proteases but due to their diminished activity. The yield of biomass from methanol was improved 1.44-fold utilizing the low-temperature strategy compared with the standard fermentation. Purification of histidine-tagged Nef was performed in one step using a Ni(2+)-nitrilotriacetate-Sepharose column. The purified product was characterized by SDS/PAGE, Western blotting, matrix-assisted laser-desorption ionization-time-of-flight MS, reversed-phase HPLC and N-terminal-sequence analysis.
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PMID:Production of recombinant HIV-1 Nef (negative factor) protein using Pichia pastoris and a low-temperature fed-batch strategy. 1655 Dec 71


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