Ent-kaurane diterpenoids from the Annonaceae family: a review of research progress and call for further research.

The Annonaceae is one of the plant families with members that are credited with numerous pharmacological functions. Among the group of compounds responsible for these bioactivities are the ent-kaurane diterpenoids. The ent-kauranes are a group of 20-Carbon, tetracyclic diterpenoids that are widely distributed in other plant families including the Annonaceae family. This mini-review focuses mainly on the ent-kaurane diterpenoids isolated from the Annonaceae family, delineates the various biological activities of these compounds, and highlights the research gaps that exist for further scientific scrutiny.

Untargeted UPLC-Q/TOF-MS-based metabolomics and inductively coupled plasma optical emission spectroscopic analysis reveal differences in the quality of ginger from two provinces in Zambia.

OBJECTIVES: This study sought to investigate the differences in the quality of dried ginger samples obtained from two places in Zambia, Lusaka and Copperbelt in terms of their secondary metabolite differences and heavy metals content. METHODS: Ten and eight batches of dried ginger obtained, respectively, from Lusaka and Copperbelt were analysed using untargeted Q/TOF-MS-based metabolomics and inductively coupled plasma optical emission spectroscopy (ICP-OES). KEY FINDINGS: The metabolomics approach yielded 11 differential metabolites that clearly discriminated between the samples from the two locations. Eight were found to be more abundant in the samples from Lusaka while three were present in greater amounts in the samples from Copperbelt. The results of the heavy metal content analysis for four selected elements, Cd, Pb, As and Cu, showed that the samples from Copperbelt recorded higher levels. However, all samples contained levels of the toxic metals, Cd and Pb above permissible limits, making them unwholesome for human consumption. CONCLUSIONS: The outcome of the heavy metal content analysis led us to speculate that abiotic stress as a result of these metals experienced by the ginger rhizomes during cultivation could have contributed to the metabolites abundance differences. Further studies are, however, recommended to verify this hypothesis.

Design, synthesis and biological evaluation of novel 3-substituted 4-anilino-coumarin derivatives as antitumor agents.

Various 3-substituted 4-anilino-coumarin derivatives have been designed, synthesized and their anti-proliferative properties have been studied. The in vitro cytotoxicity screening was performed against MCF-7, HepG2, HCT116 and Panc-1 cancer cell lines by MTT assay. Most of the synthesized compounds exhibited comparable anti-proliferative activity to the positive control 5-Fluorouracil against these four tested cancer cell lines. Among the different substituents at C-3 position of coumarin scaffold, 3-trifluoroacetyl group showed the most promising results. Especially, compounds 33d (IC50=16.57, 5.45, 4.42 and 5.16µM) and 33e (IC50=20.14, 6.71, 4.62 and 5.62µM) showed excellent anti-proliferative activities on MCF-7, HepG2, HCT116 and Panc-1 cell lines respectively. In addition, cell cycle analysis and apoptosis activation revealed that 33d induced G2/M phase arrest and apoptosis in MCF-7 cells in a dose-dependent manner. Low toxicity of compounds 33d and 33e was observed against human umbilical vein endothelial cells (HUVECs), suggesting their acceptable safety profiles in normal cells. Furthermore, the results of in silico ADME studies indicated that both 33d and 33e exhibited good pharmacokinetic properties.

Design, synthesis and evaluation of 6-aryl-indenoisoquinolone derivatives dual targeting ERα and VEGFR-2 as anti-breast cancer agents.

The estrogen receptors have played important roles in breast cancer development and progression. Selective estrogen receptor modulators, such as Tamoxifen, have showed great benefits in the treatment and prevention of breast cancer. But the disadvantages of induction of endometrial cancer and drug resistance have limited their use. Multiple ligand which act at multiple biomolecular targets may exert favorable advantages of improved efficacy with lower incidence of side effects. In this work, we described the synthesis and evaluation of a series of 6-aryl-indenoisoquinolone derivatives as dual ERα and VEGFR-2 inhibitors. These compounds presented good ERα binding affinity and ERα antagonistic activity, as well as potent VEGFR-2 inhibitory potency. They also possessed excellent anti-proliferative activities against MCF-7, MDA-MB-231, Ishikawa and HUVEC cell lines. Further investigation of selective compound 21c showed that it was able to inhibit the activation of VEGFR-2 and the signaling transduction of Raf-1/MAPK/ERK pathway in MCF-7 cells.

Anti-inflammatory and antipyretic properties of Kang 601 heji, a traditional Chinese oral liquid dosage form.

OBJECTIVE: To evaluate the scientific basis for the use of Kang 601 heji (K-601) as an anti-inflammatory and antipyretic agent using appropriate animal models. METHODS: Carrageenan-induced rat paw and xylene-induced ear oedemas were models used to investigate anti-inflammatory actions of K-601. Lipopolysaccharide-induced pyrexia model was used to evaluate antipyretic activity in Wistar rats. The anti-inflammatory and antipyretic mechanisms were evaluated by detecting prostaglandins E2, nitric oxide, interleukin-1ß and tumour necrosis factor-α levels using appropriate reagents and ELISA kits. RESULTS: The results revealed that K-601 reduced the level of inflammations in both anti-inflammatory models in a dose-dependent manner. The same was true for the antipyretic model. The possible mechanisms of actions were through the inhibition of prostaglandins E2, interleukin-1ß, tumour necrosis factor-α and nitric oxide. CONCLUSIONS: K-601 has proven anti-inflammatory and antipyretic actions. The findings provide a scientific basis for the use of K-601 as anti-inflammatory and antipyretic agent in traditional Chinese medicinal practice.

Anti-inlfammatory and antipyretic properties of kang 601 heji, a traditional Chinese medicine oral liquid dosage form

Objective:To evaluate the scientific basis for the use of Kang 601 heji (K-601) as an anti-inflammatory and antipyretic agent using appropriate animal models. Methods:Carrageenan-induced rat paw and xylene-induced ear oedemas were models used to investigate anti-inflammatory actions of K-601. Lipopolysaccharide-induced pyrexia model was used to evaluate antipyretic activity in Wistar rats. The anti-inflammatory and antipyretic mechanisms were evaluated by detecting prostaglandins E2, nitric oxide, interleukin-1βand tumor necrosis factor-αlevels using appropriate reagents and ELISA kits. Results:The results revealed that K-601 reduced the level of inflammations in both anti-inflammatory models in a dose-dependent manner. The same was true for the antipyretic model. The possible mechanisms of actions were through the inhibition of prostaglandins E2, interleukin-1β, tumor necrosis factor-αand nitric oxide. Conclusions: K-601 has proven anti-inflammatory and antipyretic actions. The findings provide a scientific basis for the use of K-601 as anti-inflammatory and antipyretic agent in traditional Chinese medicinal practice.