Synthesis of Novel 2-(Het)arylpyrrolidine Derivatives and Evaluation of Their Anticancer and Anti-Biofilm Activity

A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.

NH4Cl affects the expression of Wnt/β-catenin pathway in hepatocytes

We intended to explore whether NH4Cl influences the viability and regulates the expression of Wnt/β-catenin pathway in hepatocytes. The Chang liver cell line was used and cultured with different concentrations of NH4Cl (2.5, 5, 10, 20, 40, and 50 mmol/L) for 12, 24, and 48 h. The viability of hepatocytes was detected by MTT assay. The mRNA and protein expression level was analyzed with qRT–PCR and Western blotting, respectively. NH4Cl concentration significantly affects the viability of hepatocytes. With the increase of NH4Cl concentration, the viability of hepatocytes was decreased, accordingly. The mRNA and protein expression of Wnt1, β-catenin, and cyclin D was significantly increased after treatment with low concentrations of NH4Cl as compared with the control group, whereas their expression levels were decreased after treatment with high concentrations of NH4Cl. The mRNA and protein expression of Wnt1, β-catenin, and cyclin D was also significantly increased after treatment with NH4Cl for a short period as compared with the control group, whereas their expression levels were decreased after treatment with NH4Cl for a long period. In addition, we found NH4Cl treatment significantly reversed the results after RNA silencing of Wnt1 in hepatocytes. NH4Cl influences the viability of hepatocytes and affects the expression of Wnt/β-catenin pathway in hepatocytes.

In Vitro Assessment of Anthelmintic Activities ofRauwolfia vomitoria(Apocynaceae) Stem Bark and Roots against Parasitic Stages ofSchistosoma mansoniand Cytotoxic Study

Schistosomiasis is a Neglected Tropical Diseases which can be prevented with mass deworming chemotherapy. The reliance on a single drug, praziquantel, is a motivation for the search of novel antischistosomal compounds. This study investigated the anthelmintic activity of the stem bark and roots ofRauwolfia vomitoriaagainst two life stages ofSchistosoma mansoni. Both plant parts were found to be active against cercariae and adult worms. Within 2 h of exposure all cercariae were killed at a concentration range of 62.5–1000 µg/mL and 250–1000 µg/mL ofR. vomitoriastem bark and roots, respectively. The LC50values determined for the stem bark after 1 and 2 h of exposure were 207.4 and 61.18 µg/mL, respectively. All adult worms exposed to the concentrations range of 250–1000 µg/mL for both plant parts died within 120 h of incubation. The cytotoxic effects against HepG2 and Chang liver cell assessed using MTT assay method indicated that both plant extracts which were inhibitory to the proliferation of cell lines with IC50> 20 μg/mL appear to be safe. This report provides the first evidence of in vitro schistosomicidal potency ofR. vomitoriawith the stem bark being moderately, but relatively, more active and selective against schistosome parasites. This suggests the presence of promising medicinal constituent(s).

Effects of Oil Palm (Elais guineensis) Fruit Extracts on Glucose Uptake Activity of Muscle, Adipose and Liver Cells

The effect of oil palm (Elaeis guineensis) fruit aqueous extract (OPF) on glucose uptake activity of three different cell lines was investigated. The cell lines were incubated with different concentrations of OPF to evaluate the stimulatory effect of OPF towards glucose uptake activity of L6 myotubes, 3T3F442A adipocytes and Chang liver cell line. The glucose uptake activities of all tested cells were enhanced in the presence of OPF extract (basal condition). Nevertheless in combination of OPF extract and 100 nM insulin, the glucose uptake activity was only significantly enhanced in L6 myotubes and 3T3F442A adipocytes cell lines. The extracts enhanced the glucose uptake into cells through either insulin-mimetic or insulin-sensitizing property or combination of these two properties. It can be suggested that the OPF extract exerts its antihyperglycemic action partly by mediated glucose uptake into the glucose-responsive disposal cells, muscle, adipose and liver.