No abstract

Natural or plant products, because of their structural diversity, are a potential source for identifying new anti-hepatitis B virus (HBV) agents. Here, we report the anti-HBV activity of Euphorbia schimperi and its quercetin (QRC) and kaempferol derivatives. The anti-HBV-active methanol fraction of E. schimperi was subjected to chromatographic techniques, leading to isolation of three flavonols, following their structure determination by 1 H and 13 C NMR spectroscopies. Their cytotoxicity and anti-HBV potential were assessed using HBV reporter HepG2.2.15 cells, and their modes of action were delineated by molecular docking. The isolated compounds identified as quercetin-3-O-glucuronide (Q3G), quercetin-3-O-rhamnoside (Q3R), and kaempferol-3-O-glucuronide (K3G) were non-cytotoxic to HepG2.2.15 cells. The viral HBsAg/ HBeAg production on day 5 was significantly inhibited by K3G (∼70.2/∼73.4%), Q3G (∼67.8/∼72.1%), and Q3R (∼63.2%/ ∼68.2%) as compared to QRC (∼70.3/∼74.8%) and lamivudine (∼76.5/∼84.5%) used as standards. The observed in vitro anti-HBV potential was strongly supported by in silico analysis, which suggested their structure-based activity via interfering with viral Pol/RT and core proteins. In conclusion, this is the first report on the anti-HBV activity of E. schimperi-derived quercitrin-3-Oglucuronide, quercitrin-3-O-rhamnoside, and kaempferol-3-O-glucuronide, most likely through interfering with HBV proteins.

Leishmaniasis is a fatal neglected parasitic disease caused by protozoa of the genusLeishmaniaand transmitted to humans by different species ofphlebotominesandflies. The disease incidence continues to increase due to lack of vaccines and prophylactic drugs. Drugs commonly used for the treatment are frequently toxic and highly expensive. The problem of these drugs is further complicated by the development of resistance. Thus, there is an urgent need to develop new antileishmanial drug candidates. The aim of this study was to synthesize certain quinoline-4-carboxylic acids, confirm their chemical structures, and evaluate their antileishmanial activity. Pfitzinger reaction was employed to synthesize fifteen quinoline-4-carboxylic acids (Q1-Q15) by reacting equimolar mixtures of isatin derivatives and appropriateα-methyl ketone. The products were purified, and their respective chemical structures were deduced using various spectral tools (IR, MS,1H NMR, and13C NMR). Then, they were investigated againstL. donovanipromastigote (clinical isolate) in different concentration levels (200 μg/mL to 1.56 μg/mL) against sodium stibogluconate and amphotericin B as positive controls. The IC50for each compound was determined and manipulated statistically. Among these compounds,Q1(2-methylquinoline-4-carboxylic acid) was found to be the most active in terms of IC50.

Bioactive natural or phytoproducts have emerged as a potential source of antiviral agents. Of the Rhus spp., R. coriaria and R. succedanea have been reported for their antiviral activities against hepatitis B virus (HBV), while the anti-HBV efficacy of R. tripartita has remained elusive. In the present study, the anti-HBV activities of R. tripartita-derived novel catechin [3,5,13,14-flavantetrol-catechin or rhuspartin (RPT)] and epicatechin-3-O-rhamnoside (ECR), were assessed using the HBV-reporter cell line HepG2.2.15. RPT and ECR proved to efficiently inhibit HBV surface antigen (HBsAg) synthesis by 68.8 and 71.3%, respectively, and HBV pre-core antigen (HBeAg) production by 62.3 and 71.2%, respectively, after 5 days of treatment. Of note, RPT had a lower anti-HBV activity than ECR. In comparison, the reference drug lamivudine (LAM) inhibited HBsAg and HBeAg expression by 83.6 and 85.4%, respectively. Further molecular docking analysis revealed formations of strong complexes of RPT, ECR and LAM with HBV polymerase through interactions with binding pocket residues. Taken together, the present results demonstrated promising therapeutic potential of the novel R. tripartita-derived catechin and epicatechin for HBV, warranting their further molecular and pharmacological evaluation.