Finally, an optimal compound, PIF_9, was identified. Then, all target compounds were subjected to their structure–activity relationships (SAR) screening of anti-inflammatory activity in mouse mononuclear macrophage RAW264.7 cell line, and their cytotoxicities were determined after.
#Finely home by ben markly series
Firstly, based on the strategy of pharmacophore combination, indanone moiety was introduced onto the pterostilbene skeleton to generate a novel series of pterostilbene derivatives (PIF_1–PIF_16) which could possess both anti-oxidative and anti-inflammatory activities for sepsis treatment. Starting from it, we have made several rounds of rational optimizations. Pterostilbene, which exerts attractive anti-oxidative and anti-inflammatory activities, is a homologue of natural polyphenolic derivative of resveratrol. It is still in urgent need of new effective therapeutic agents, and chances are great that some candidates can be identified that can attenuate oxidative stress and inflammatory responses. Sepsis remains one of the most common life-threatening illnesses that is characterized by a systemic inflammatory response syndrome (SIRS) and usually arises following severe trauma and various septic infections. This study supports the potential use of resveratrol, pterostilbene or related compounds as adjuvants in anti-HIV pre-exposure prophylaxis (PrEP) formulations. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, a simian immunodeficiency virus protein that increases dNTP levels.
Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Resveratrol has been shown to inhibit replication of several viruses, including herpes simplex 1 and 2, papillomaviruses, SARS virus and influenza virus. Resveratrol and pterostilbene are plant stilbenoids associated with several health promoting benefits.
HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion.
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