Изследване на новосинтезирани стирилхинолини за анти-HIV-1 активност в клетъчна култура : [Автореферат] /
Earlier it has been reported about anti-HIV-1 integrase activity of styryl-quinolines (Mekouar K. et al., 1998). In Bulgaria six novel 2-styryl-8-hydroxyquinolines (8SQs) derivatives were synthesized and evaluated for anti-HIV-activity in cell culture (105B, 208, 241, 242,300S and 303S). The aim of...
| Основен автор: | Хинков, Антон Веселинов 1981- |
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| Други автори: | Hinkov, Anton Veselinov 1981-, Аргирова, Радка Младенова 1944- (науч. ръководител) |
| Формат: | Книга |
| Език: | Bulgarian |
| Публикувано: |
София,
2012.
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Пълен текст |
| Резюме: |
Earlier it has been reported about anti-HIV-1 integrase activity of styryl-quinolines (Mekouar K. et al., 1998). In Bulgaria six novel 2-styryl-8-hydroxyquinolines (8SQs) derivatives were synthesized and evaluated for anti-HIV-activity in cell culture (105B, 208, 241, 242,300S and 303S). The aim of this work was to target anti-HIV-1 activity of novel substances. Supernatants of chronically infected H9/HTLVIIIB were used as a source of HIV-1. Cytotoxicity tests and microtiter infection assays for HIV cytopathic effect in MT4 cells were performed (MTT uptake assay). Reverse transcriptase (RT) activity in supernatants and directly on recombinant RT (Cavidi, Sweden) were checked. Protease as a target was studied by modified screening method using direct spectrophotometric reading of specific substrate utilization by native HIV-1 protease in the absence and presence of the substances studied. 300S and 303S demonstrate antiprotease activity. To check the integrase as a target, mutants were obtained by serial passaging of virus with continuous exposure to increasing concentrations of active compounds followed by sequencing of in region. Mitochondrial toxicity was evaluated by RealTime-PCR as mtDNA:nDNA ratio. Two novel 8SQs: 105B and 241, differing in substitutes at C2 in the phenol ring, demonstrated inhibition of HIV replication (105B -95 and 241-70).105B showed mitochondrial toxicity accompanied by reducing of both mtDNA and nDNA (mtDNA:nDNA = 0.82 compared to 1.01 and 0.97 in MT4 uninfected and HIV-1 infected cells without inhibitor, resp.). 241 showed no mitochondrial toxicity. Both derivatives exposed no RT inhibition but anti-protease activity (105B-21 and 241-25 resp.). As far as the latter did not explain anti-HIV effect in microtiter assay, we looked for mutations in IN gene in passages 30-32 for 105B and 241. The molecular sequencing found mutations in 105B (N17S, D231I) and in 241 (E10D, D231I), all in in region. |
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| Физически характеристики: |
48 с. : с ил. ; 21 см. |