Paeonol repurposing for cancer therapy: From mechanism to clinical translation.

Paeonol (PAE) is a natural phenolic monomer isolated from the root bark of Paeonia suffruticosa that has been widely used in the clinical treatment of some inflammatory-related diseases and cardiovascular diseases. Much preclinical evidence has demonstrated that PAE not only exhibits a broad spectrum of anticancer effects by inhibiting cell proliferation, invasion and migration and inducing cell apoptosis and cycle arrest through multiple molecular pathways, but also shows excellent performance in improving cancer drug sensitivity, reversing chemoresistance and reducing the toxic side effects of anticancer drugs. However, studies indicate that PAE has the characteristics of poor stability, low bioavailability and short half-life, which makes the effective dose of PAE in many cancers usually high and greatly limits its clinical translation. Fortunately, nanomaterials and derivatives are being developed to ameliorate PAE's shortcomings. This review aims to systematically cover the anticancer advances of PAE in pharmacology, pharmacokinetics, nano delivery systems and derivatives, to provide researchers with the latest and comprehensive information, and to point out the limitations of current studies and areas that need to be strengthened in future studies. We believe this work will be beneficial for further exploration and repurposing of this natural compound as a new clinical anticancer drug.

Structurally diverse isoquinoline and amide alkaloids with dopamine D2 receptor antagonism from Corydalis bungeana.

Four new isoquinoline alkaloids including a benzophenanthridine alkaloid (1), a morphine derivative (2), a narceine-type alkaloid (3) and a simple isoquinoline alkaloid (4), a new amide alkaloid (5) and a new phthalic acid derivative (6), together with eleven known alkaloids (7-17) were obtained from the whole herbs extract of Corydalis bungeana Turcz. Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-17 were evaluated for dopamine D2 receptor activity in CHO-D2 cells. Among them, 16 showed the highest antagonistic activity on the D2 receptor with an IC50 value of 2.04 ± 0.01 µM. Compounds 14 and 15 exhibited moderate antagonism with IC50 values of 13.66 ± 2.28 and 31.72 ± 2.52 µM, respectively.