Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways.

A series of quillaic acid derivatives with different substituents on the 28-carboxyl group were designed and synthesized. Five human cancer cell lines (HCT116, BEL7402, HepG2, SW620, and MCF-7) were evaluated for their antitumor activity in vitro. Some of the tested derivatives showed improved antiproliferative activity compared to the lead compound, quillaic acid. Among them, compound E (IC50 = 2.46 ± 0.44 µM) showed the strongest antiproliferative activity against HCT116 cells; compared with quillaic acid (IC50 > 10 µM), its efficacy against HCT116 cancer cells was approximately 4-fold higher than that of quillaic acid. Compound E also induces cell cycle arrest and apoptosis by modulating NF-κB and MAPK pathways. Therefore, the development of compound E is certainly valuable for anti-tumor applications.

Anti-hypertensive and endothelia protective effects of Fufang Qima capsule on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway.

OBJECTIVE: To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule. METHODS: Spontaneous hypertensive rats (SHRs) were used to study the underlying mechanism of the anti-hypertension activity of QM. In this study, SHRs were randomly divided into 5 groups: model group, Telmisartan group (7.2 mg/kg, p.o.), and three QM groups (0.9298, 1.8596, and 3.7192 g/kg, p.o.). Wistar Kyoto rats (WKY) were used as normal control group. Blood pressure (BP), aorta, perivascular adipose tissue (PVAT) histology were investigated to evaluate the effect of QM. Nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) phosphorylation were measured. Adiponectin (APN) secretion, as well as APN signal pathway proteins including APN, adiponectin receptors (R1 and R2) and adenosine 5'-monophosphate-activated protein kinase (AMPK) were all analyzed. RESULTS: QM significantly reduced BP and ameliorated the vascular pathological change, i.e. intima media thicken and collagen fiber hyperplasia. Meanwhile, QM increased concentration of NO and the phosphorylation of eNOS in the aorta. The anti-hypertensive and endothelia-protective effect of QM could be attributed to activating APN/ AMPK pathway by up-regulating the expression of APN in PVAT and APN Receptor 2, AMPKα and phosphorylated AMPKα in the aorta. CONCLUSION: The QM alleviation effect mechanism for primary hypertension was via modulating the APN/AMPK signal pathway.

Evaluation of ursolic acid derivatives with potential anti-Toxoplasma gondii activity.

Toxoplasma gondii is an important pathogen that causes serious public health problems. Currently, therapeutic drugs for toxoplasmosis cause serious side effects, and more effective and novel substances with relatively low toxicity are urgently needed. Ursolic acid (UA) has many properties that can be beneficial to healthcare. In this study, we synthesized eight series of UA derivatives bearing a tetrazole moiety and evaluated their anti-T. gondii activity in vitro using spiramycin as a positive control. Most of the synthesized derivatives exhibited better anti-T. gondii activity in vitro than UA, among which compound 12a exhibited the most potent anti-T. gondii activity. Furthermore, the results of biochemical parameter determination indicated that 12a effectively restored the normal body weight of mice infected with T. gondii, reduced hepatotoxicity, and exerted significant anti-oxidative effects compared with the findings for spiramycin. Additionally, our molecular docking study indicated that the synthesized compounds could act as potential inhibitors of T. gondii calcium-dependent protein kinase 1 (TgCDPK1), with 12a possessing strong affinity for TgCDPK1 via binding to the key amino acids GLU129 and TYR131.

Value of cystatin C in predicting atrial fibrillation recurrence after radiofrequency catheter ablation.

BACKGROUD: Recent studies have demonstrated that cystatin C is a valuable risk marker for cardiovascular disease morbidity and mortality. Therefore, we hypothesized that the pre-ablation cystatin C level was associated with post-ablation atrial fibrillation (AF) recurrence. METHODS: 207 patients were enrolled and completed in this prospective observational study. Patients with AF scheduled for receive radiofrequency catheter ablation (RFCA) therapy were screened for the study. Before ablation therapy, electrocardiogram, 24 h holter monitor, transesophageal echocardiography, serum cystatin C, high-sensitivity C-reactive protein, creatinine levels, and routine blood examinations were examined. After ablation, patients were followed up every week for the first month, and then at 2, 3, 6, 9, and 12 months. Thereafter, patients came back to out-patient clinic every six months regularly. Electrocardiogram or 24 h holter monitor were repeated if the patient experienced palpitations or every six months. AF recurrence was defined as atrial fibrillation/atrial flutter or atrial tachycardia lasting ≥ 30 seconds within three months after therapy. RESULTS: Compared to patients with no AF recurrence, patients with recurrence had longer AF history (P = 0.007), more early recurrence (P = 0.000), a larger left atrium (P = 0.004), and higher pre-ablation cystatin C levels (P = 0.000). Multivariate regression analysis revealed that cystatin C and left atria (LA) diameter were risk factors for AF recurrence. After adjusting for LA diameter, the risk of AF recurrence increased 30% with every milligram cystatin C elevation (95% CI: 1.117-1.523). CONCLUSIONS: Pre-ablation cystatin C levels were associated with AF recurrence after RFCA therapy, an optimal cut-off value of 1.190 mg/L (sensitivity = 0.576; specificity = 0.851).

Synthesis and antiproliferative activity of 1,4-bis(dimethylamino)-9,10-anthraquinone derivatives against P388 mouse leukemic tumor cells.

A series of 2-substituted-1,4-bis(dimethylamino)-9,10-anthraquinone derivatives were synthesized and their in vitro antiproliferative activities against p388 mouse leukemic tumor cells were evaluated. In addition, the effect of substituents on the phenyl ring was investigated. Among the derivatives tested, seven showed a high antiproliferative effect and three showed a moderate effect. In addition, introduction of a series of substituted phenyl groups into 1,4-bis(dimethylamino)-9,10-anthraquinone at 2-position were shown to enhance its antiproliferative activity. The antiproliferative activity also increased upon substitution of the benzene ring by an electron donating group such as an amine or methoxyl group.