AI Article Synopsis
- A variety of quinoline compounds have been shown to have pharmaceutical effects, particularly against HIV-1, with specific derivatives like 2-styrylquinolines and 8-hydroxyquinolines inhibiting the HIV-1 integrase enzyme.
- Researchers synthesized thirty-one new quinoline derivatives, testing them for their effectiveness against HIV-1, and found that Compound 31 demonstrated the highest antiviral activity in cell assays.
- Further tests indicated that Compound 31 is effective in inhibiting both virus entry and cell fusion, showing strong potential as an anti-HIV-1 treatment compared to existing inhibitors.
Article Abstract
A plenty of natural products and synthetic derivatives containing quinoline moiety have been reported to possess various pharmacological activities. Quinolines such as 2-styrylquinolines and 8-hydroxyquinolines are extensively studied for their anti-HIV-1 activity and found to act mainly through HIV-1 integrase enzyme inhibition. In continuation of our efforts to search for newer anti-HIV-1 molecules, thirty-one quinoline derivatives with different linkers to ancillary phenyl ring were synthesized and evaluated for in vitro anti-HIV-1 activity using TZM-bl assays. Compound 31 showed higher activity in TZM-bl cell line against HIV-1 and HIV-1 cell associated virus (IC 3.35 ± 0.87 and 2.57 ± 0.71 μM) as compared to other derivatives. Compound 31 was further tested against cell free virus HIV-1 and HIV-1 (IC 1.27 ± 0.31 and 2.88 ± 1.79 μM, TI 42.20 and 18.61, respectively). This lead molecule also showed good activity in viral entry inhibition assay and cell fusion assay defining its mode of action. The activity of compound 31 was confirmed by testing against HIV-1 in activated peripheral blood mononuclear cells (PBMCs). Binding interactions of 31 were compared with known entry inhibitors.
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| http://dx.doi.org/10.1016/j.bioorg.2018.07.016 | DOI Listing |
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