ABSTRACT
In this study, azvudine (FNC), hydrochloride salt of azvudine (FNC-HCl) and triphosphate azovudine (FNC-TP) were tested against DENV-Ⅱ recombinant virus (DENV-Ⅱ Luc+). The inhibitory activity of FNC, FNC-HCl and FNC-TP on DENVs were detected by plaque assay. The effect on the expression of DENV-Ⅱ envelope protein E was detected by Western blot; the inhibitory of DENV-Ⅱ viral RNA by compounds was detected by real-time quantitative PCR. MTT assay was used to determine the cytotoxicity of the three compounds on Vero cells. The results showed that FNC, FNC-HCl and FNC-TP inhibited the viral replication by inhibition of renilla luciferase activity of DENV-Ⅱ Luc+. The 50% effective concentration (EC50) of FNC, FNC-HCl and FNC-TP in the inhibition of DENVs replication were from 0.54-25.42 μmol·L-1, while that of ribavirin was 40.78 ±1.02 μmol·L-1 as the positive control. Western blot and real time quantitative PCR results showed that FNC, FNC-HCl and FNC-TP significantly inhibited the expression of DENV-Ⅱ E protein, and the replication of DENV-Ⅱ viral RNA. The 50% cytotoxic concentrations of FNC, FNC-HCl and FNC-TP were all greater than 3 000.00 μmol·L-1. The results suggest that in vitro anti-DENVs activities of FNC, FNC-HCl and FNC-TP are superior to ribavirin, which are expected to become new candidates of anti-DENV drugs.
ABSTRACT
Tepoxalin is a potent inhibitor of both the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, as well as a potent anti-inflammatory and control-pain (postoperation, arthritis et. al.) agent. The new method about the use of novel synthesis reagents and the first using ionic liquid as reactive solvent to synthesize tepoxalin were presented in this paper. The ionic liquid can be easily recycled and reused for several runs efficiently. The analgesic activity of tepoxalin was detected by acetic acid test on mice. The analysis of variance showed that oral administration of tepoxalin could significantly inhibit the number of writhing response within 1 hour and prolong the latent time in a dose dependent manner as compared with CMC control group (P < 0.05). At the same time, tepoxalin had the same analgesic activity as diclofenac sodium.
Subject(s)
Animals , Mice , Administration, Oral , Analgesics , Pharmacology , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Cyclooxygenase Inhibitors , Pharmacology , Diclofenac , Pharmacology , Imidazoles , Chemistry , Ionic Liquids , Chemistry , Lipoxygenase Inhibitors , Pharmacology , Pain Measurement , Pyrazoles , Pharmacology , Random AllocationABSTRACT
<p><b>AIM</b>A series of new 1,4-pentadien-3-one derivatives were synthesized to search for new Eight novel hydroxylated non-steroidal anti-inflammatory drugs (NSAIDs) with potent activity.</p><p><b>METHODS</b>E,E-1-(3'-indolyl)-5-( substituted phenyl)-1,4-pentadien-3-one derivatives were synthesized by means of aldol condensation and characterized by 1H NMR, ESI-MS and element analysis. Their anti-inflammatory activity in vitro were evaluated.</p><p><b>RESULTS</b>Preliminary in vitro pharmacological tests showed that all compounds exhibited anti-inflammatory activity.</p><p><b>CONCLUSION</b>Compounds 4d and 4e exhibited potent anti-inflammatory activity and their anti-inflammatory activity was comparable to resveratrol, and were worthy of further study.</p>