•A series of novel sulfonamide derivatives were synthesized.•The antiproliferative activities against four cancer cell lines were determined.•These compounds exert antitumor effect via tubulin depolymerization.•BA-3b was very potent against both drug-sensitive and MDR cancer cell lines.A series of benzenesulfonamide derivatives were synthesized and evaluated for their anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferative and tubulin polymerization. Compound BA-3b proved to be the most potent compound with IC50 value ranging from 0.007 to 0.036 μM against seven cancer cell lines, and three drug-resistant cancer cell lines, which indicated a promising anti-cancer agent. The target tubulin was also verified by dynamic tubulin polymerization assay and tubulin intensity assay.

Traditional herbal medicines have been reported to possess significant bioactivities. In this investigation, a combined strategy using both phytochemical and biological approaches was conducted to discern the effective components of licorice, a widely used herbal medicine. Altogether, 122 compounds (1–122), including six new structures (1–6), were isolated and identified from the roots and rhizomes of Glycyrrhiza uralensis (licorice). These compounds were then screened using 11 cell- and enzyme-based bioassay methods, including Nrf2 activation, NO inhibition, NF-κB inhibition, H1N1 virus inhibition, cytotoxicity for cancer cells (HepG2, SW480, A549, MCF7), PTP1B inhibition, tyrosinase inhibition, and AChE inhibition. A number of bioactive compounds, particularly isoprenylated phenolics, were found for the first time. Echinatin (7), a potent Nrf2 activator, was selected as an example for further biological work. It attenuated CCl4-induced liver damage in mice (5 or 10 mg/kg, ip) and thus is responsible, at least in part, for the hepatoprotective activity of licorice.

•Biotransformation of 20(R)-panaxadiol yielded seven compounds.•Rhizopus chinensis catalyzes hydroxylation and further dehydrogenation at C-24.•R. chinensis also catalyzes hydroxylation at C-7, C-15, C-16, and C-29.•Three of these metabolites moderately inhibit growth of HepG2 cells.•Three of these metabolites also moderately inhibited the NF-κB transcriptional activity.Microbial transformation of 20(R)-panaxadiol by the fungus Rhizopus chinensis CICC 3043 yielded seven metabolites. Their structures were elucidated on the basis of extensive spectroscopic analyses. R. chinensis could catalyze hydroxylation and further dehydrogenation at C-24 of 20(R)-panaxadiol, as well as hydroxylation at C-7, C-15, C-16, and C-29. Three of these compounds at 10 μM could moderately inhibit growth of HepG2 human hepatocellular carcinoma cells with an inhibition rate of about 40%. Three compounds (also at 10 μM) showed approximately 30% inhibition on NF-κB transcriptional activity in SW480 human colon carcinoma cells stably transfected with NF-κB luciferase reporter and induced by LPS.Biotransformation of 20(R)-panaxadiol (1) by the fungus Rhizopus chinensis CICC 3043 yielded seven metabolites, including (2). The biotransformation reactions included hydroxylation and further dehydrogenation.

Endoplasmic reticulum (ER) stress induced by free fatty acids (FFA) is important to β-cell loss during the development of type 2 diabetes. To test whether vanadium compounds could influence ER stress and the responses in their mechanism of antidiabetic effects, we investigated the effects and the mechanism of vanadyl bisacetylacetonate [VO(acac)2] on β cells upon treatment with palmitate, a typical saturated FFA. The experimental results showed that VO(acac)2 could enhance FFA-induced signaling pathways of unfolded protein responses by upregulating the prosurvival chaperone immunoglobulin heavy-chain binding protein/78-kDa glucose-regulated protein and downregulating the expression of apoptotic C/EBP homologous protein, and consequently the reduction of insulin synthesis. VO(acac)2 also ameliorated FFA-disturbed Ca2+ homeostasis in β cells. Overall, VO(acac)2 enhanced stress adaption, thus protecting β cells from palmitate-induced apoptosis. This study provides some new insights into the mechanisms of antidiabetic vanadium compounds.

•Nrf2 deficiency deteriorated CTX-induced myelosuppression in vitro/in vivo.•Nrf2 deficiency decreased antioxidant capacity of peripheral blood and bone marrow.•Nrf2 deficiency impaired hematopoietic proliferating and colony formation ability.•CDDO-Me Nrf2-dependently mitigated CTX-induced myelosuppression.Myelosuppression is the most common dose-limiting adverse effect of chemotherapies. In the present study, we investigated the involvement of nuclear erythroid 2-related factor 2 (Nrf2) in cyclophosphamide-induced myelosuppression in mice, and evaluated the potential of activating Nrf2 signaling as a preventive strategy. The whole blood from Nrf2−/− mice exhibited decreased antioxidant capacities, while the bone marrow cells, peripheral blood mononuclear cells and granulocytes from Nrf2−/− mice were more susceptible to acrolein-induced cytotoxicity than those from wild type mice. Single dosage of cyclophosphamide induced significantly severer acute myelosuppression in Nrf2−/− mice than in wild type mice. Furthermore, Nrf2−/− mice exhibited greater loss of peripheral blood nucleated cells and recovered slower from myelosuppression nadir upon multiple consecutive dosages of cyclophosphamide than wild type mice did. This was accompanied with decreased antioxidant and detoxifying gene expressions and impaired colony formation ability of Nrf2−/− bone marrow cells. More importantly, activation of Nrf2 signaling by CDDO-Me significantly alleviated cyclophosphamide-induced myelosuppression, while this alleviation was diminished in Nrf2−/− mice. In conclusion, the present study shows that Nrf2 plays a protective role in cyclophosphamide-induced myelosuppression and activation of Nrf2 is a promising strategy to prevent or treat chemotherapy-induced myelosuppression.

•Molecular mechanisms for cytotoxic activity of licoricidin (LCD) were investigated.•LCD promoted autophagy of SW480 cells through AMPK and Akt/mTOR signaling pathways.•Both LCD and its glucoside showed in vivo anti-colorectal cancer activities.Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC50 value of 7.2 μM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling. Meanwhile, LCD promoted autophagy in SW480 cells, and activated AMPK signaling and inhibited Akt/mTOR pathway. Overexpression of a dominant-negative AMPKα2 abolished LCD-induced inhibition of Akt/mTOR, autophagic and pro-apoptotic signaling pathways, and significantly reversed loss of cell viability, suggesting activation of AMPK is essential for the anti-cancer activity of LCD. In vivo anti-tumor experiments indicated that LCD (20 mg/kg, i.p.) significantly inhibited the growth of SW480 xenografts in nude mice with an inhibitory rate of 43.5%. In addition, we obtained the glycosylated product LCDG by microbial transformation, and found that glycosylation slightly enhanced the in vivo anti-cancer activities of LCD. This study indicates that LCD could inhibit SW480 cells by inducing cycle arrest, apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic agent against colorectal cancer.Download high-res image (208KB)Download full-size image