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anti-HIV-1 Activity (anti-hiv-1 + activity)
Selected AbstractsPredicting Anti-HIV-1 Activities of HEPT-analog Compounds by Using Support Vector ClassificationMOLECULAR INFORMATICS, Issue 9 2005Wencong Lu Abstract The support vector classification (SVC), as a novel approach, was employed to make a distinction within a class of non-nucleoside reverse transcriptase inhibitors. 1-[(2-hydroxyethoxy) methyl]-6-(phenyl thio)-thymine (HEPT) derivatives with high anti-HIV-1 activities and those with low anti-HIV-1 activities were compared on the basis of the following molecular descriptors: net atomic charge on atom 4, molecular volume, partition coefficient, molecular refractivity, molecular polarisability and molecular weight. By using the SVC, a mathematical model was constructed, which can predict the anti-HIV-1 activities of the HEPT-analogue compounds, with an accuracy of 100% as calculated on the basis of the leave-one-out cross-validation (LOOCV) test. The results indicate that the performance of the SVC model exceeds that of the stepwise discriminant analysis (SDA) model, for which a prediction accuracy of 94% was reported. [source] Synthesis and Anti-HIV-1 Activity of 1-Substiuted 6-(3-Cyanobenzoyl) and [(3-Cyanophenyl)fluoromethyl]-5-ethyl-uracilsARCHIV DER PHARMAZIE, Issue 9 2009Yasser M. Loksha Abstract 1-Substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils were synthesized and evaluated in cell-based assays against HIV-1 wild-type and its clinically relevant non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants. Some of the synthesized compounds showed activity against HIV-1 wild-type in the same range as Emivirine (MKC-442). 3-{[3-(Allyloxymethyl)-5-ethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]fluoromethyl}-benzonitrile 11b showed moderate activity against the Y181C HIV-1 mutant strain. [source] Computed molecular surface electrostatic potentials of two groups of reverse transcriptase inhibitors: Relationships to anti-HIV-1 activitiesINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3-4 2001Oscar Galvez Gonzalez Abstract We have used the GIPF approach (general interaction properties function) to develop analytical representations for the anti-HIV-1 potencies of two groups of reverse transcriptase inhibitors. Their activities are expressed in terms of certain statistical properties of their molecular surface electrostatic potentials, computed at the HF/STO-5G*//HF/STO-3G* level. The results provide insight into some of the factors that promote inhibition. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 115,121, 2001 [source] Predicting Anti-HIV-1 Activities of HEPT-analog Compounds by Using Support Vector ClassificationMOLECULAR INFORMATICS, Issue 9 2005Wencong Lu Abstract The support vector classification (SVC), as a novel approach, was employed to make a distinction within a class of non-nucleoside reverse transcriptase inhibitors. 1-[(2-hydroxyethoxy) methyl]-6-(phenyl thio)-thymine (HEPT) derivatives with high anti-HIV-1 activities and those with low anti-HIV-1 activities were compared on the basis of the following molecular descriptors: net atomic charge on atom 4, molecular volume, partition coefficient, molecular refractivity, molecular polarisability and molecular weight. By using the SVC, a mathematical model was constructed, which can predict the anti-HIV-1 activities of the HEPT-analogue compounds, with an accuracy of 100% as calculated on the basis of the leave-one-out cross-validation (LOOCV) test. The results indicate that the performance of the SVC model exceeds that of the stepwise discriminant analysis (SDA) model, for which a prediction accuracy of 94% was reported. [source] Concentricolide, an Anti-HIV Agent from the Ascomycete Daldinia concentricaHELVETICA CHIMICA ACTA, Issue 1 2006Xiang-Dong Qin Abstract A novel benzofuran lactone, named concentricolide (=,rel -(6R)-6-ethylbenzo[2,1- b:3,4- c,]difuran-8(6H)-one; 1), was isolated along with four known compounds (friedelin, cytochalasin L-696,474, armillaramide, and russulamide) from the fruiting bodies of the xylariaceous ascomycete Daldinia concentrica. The structure of 1 was established by spectroscopic methods and X-ray crystallographic analysis. Its anti-HIV-1 activity was tested. Results showed that 1 inhibited HIV-1 induced cytopathic effects. The EC50 value was 0.31,,g/ml. The therapeutic index (TI) was 247. Concentricolide exhibited the blockage (EC50 0.83,,g/ml) on syncytium formation between HIV-1 infected cells and normal cells. [source] Synthesis and anti-HIV-1 activity of 1,3-phenylene bis-uracil analogues of MKC-442JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2007Youssef L. Aly Reaction of 1,3-phenylenediacetonitrile with the zinc organometallic reagent of ethyl 2-bromobutyrate afforded the 1,3-phenylene-bis(acetoacetate) 2 which was used as the starting material for the synthesis of 1,3-phenylene-bis[6-(2-thiouracil)] 4. Desulphurization of 4 gave the corresponding bis-uracil 6, which after silylation was N-1 alkylated with bis(allyoxy)methane using TMS-triflate as the catalyst or with chloromethyl ethyl ether to give the MKC-442 analogues 7 and 9. The amino-DABO and S-DABO derivatives 11, 12a,b and 14 were also synthesized. The anti-HIV-1 activity test showed that when MKC-442 analogues were constructed with 1,3-phenylene in all cases they were detrimental to have activity against HIV-1. [source] Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infectionMEDICINAL RESEARCH REVIEWS, Issue 1 2004Robert H. Cichewicz Abstract 3,-Hydroxy-lup-20(29)-en-28-oic acid (betulinic acid) is a pentacyclic lupane-type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti-inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti-HIV-1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti-HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti-HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post-binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV-1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma-derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non-melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 90,114, 2004 [source] Anti-HIV-1 constituents from Clausena excavata: Part II. carbazoles and a pyranocoumarinPHYTOTHERAPY RESEARCH, Issue 8 2005Boonsong Kongkathip Abstract Three carbazole derivatives, O -methylmukonal (1), 3-formyl-2,7-dimethoxycarbazole (2) and clauszoline J (3), and a pyranocoumarin, clausenidin (4), were isolated from the rhizomes and roots of Clausena excavata. Compound 1, isolated from this plant for the first time, has not been reported previously as having anti-HIV-1 activity. Compounds 1,4 displayed anti-HIV-1 activity in a syncytial assay with EC50 values of 12, 29.1, 34.2 and 5.3 µm, respectively, and thus exhibited potential therapeutic index (PTI) values of 56.7, 8.0, 1.6 and 7.0, respectively. All isolated compounds demonstrated a lack of cytotoxicity against the KB and BC-1 cancer cell lines. Copyright © 2005 John Wiley & Sons, Ltd. [source] Inhibitory effects of Korean plants on HIV-1 activitiesPHYTOTHERAPY RESEARCH, Issue 6 2001Byung Sun Min Abstract In the search for novel anti-human immunodeficiency virus type 1 (anti-HIV-1) agents from natural sources, 49 MeOH extracts of Korean plants were screened for their inhibitory effects against RNA-dependent DNA polymerase (RT) and ribonuclease H (RNase H) activities of HIV-1 reverse transcriptase and HIV-1 protease, and anti-HIV-1 activity. Regarding the HIV-1 reverse transcriptase, Agrimonia pilosa (whole plant), Cornus kousa (stem and leaf), Limonium tetragonum (root) and Mallotus japonicus (stem) showed significant inhibitory activity on RT activity with 50% inhibitory activity (IC50) of 8.9, 6.3, 7.5 and 11.9,µg/mL, respectively, whereas Agrimonia pilosa was also active against RNase H activity (IC50,=,98.4,µg/mL). Four plants, namely Agrimonia pilosa (whole plant), Atractylodes japonica (root), Clematis heracleifolia (whole plant) and Syneilesis palmata (whole plant), were appreciably active (<35%) against recombinant HIV-1 protease at a concentration of 100,µg/mL. Crinum asiaticum var. japonicum (root) showed significant anti-HIV-1 activity (ED50,=,12.5,µg/mL) with a favourable SI value of 16. Copyright © 2001 John Wiley & Sons, Ltd. [source] | ||||||||||