Paeoniflorigenone purified from Paeonia daurica roots potently inhibits viral and bacterial DNA polymerases: investigation by experimental validation and docking simulation

AbstractThe methanolic extracts from fruit, leaf, stem and roots ofPaeonia daurica subsp. macrophylla (P. daurica) were investigated for inhibitory effect on replicative bacterial (PolC and DnaE2) and viral (MMLV-RT from Moloney Murine Leukemia Virus) DNA polymerases by primer extension assay. While all plant parts showed inhibition effect on bacterial and viral DNA polymerases, roots of the plant was focused to purify inhibitory compound(s). The chemical structures of compounds were completely elucidated using a combination of NMR, MS and FT-IR analyses. Five molecules with tree monoterpene glycosides, paeoniflorin (PD-2), paeoniflorigenone (PD-4), benzoyl paeoniflorin (PD-5), and benzoic acid (PD-3) with its derivate 2,4,6-trihydroxy-1-methyl benzoate (PD-1) were purified and identified. Both DNAdependent and RNA-dependent polymerase activity of MMLV-RT was strongly inhibited by these five molecules. On the other hand, bacterial polymerases PolC and DnaE2 were strongly inhibited by only paeoniflorigenone (PD-4). Molecular modeling result suggested that paeoniflorigenone (PD-4) interacts with the important residues at active site (palm, fingers and thumb domains) of three polymerases which support our experimental result. Ethyl acetate fraction had smallest SC50 value against DPPH and ABTS radicals. It showed also higher scavenging activity than quercetin, trolox and ascorbic acid since its quite high total phenolic content. We proposed that the parts ofP. daurica might be u...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research

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Acute myeloid leukemia (AML) is the fifth most common malignancy in children, and the prognosis for AML in children remains relatively poor. However, its incidence and survival trends based on a large sample size have not been reported.Children diagnosed with AML between 1975 and 2014 were accessed from the Surveillance, Epidemiology, and End Results database. Incidence and survival trends were evaluated by age-adjusted incidence and relative survival rates (RSRs) and Kaplan-Meier analyses. Cox regression was performed to identify independent risk factors for child AML death.The overall incidence of AML in childhood increa...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Conclusions: Prognostic lncRNA-LOC646762, which may contribute to AML through the "endocytosis" signaling pathway, may act as a biomarker for predicting the survival of adult AML patients, as well as for risk stratification.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Acute myeloid leukemia (AML) is an aggressive malignancy lacking targeted therapy due to shared molecular and transcriptional circuits as well as phenotypic markers with normal hematopoietic stem cells (HSCs). Identifying leukemia specific markers expressed on AML or AML subtypes for therapeutic targeting is of exquisite clinical value. Here we show that CD4, a T lymphocytes membrane glycoprotein that interacts with major histocompatibility complex class II antigens and is also expressed in certain AML subsets but not on HSCs is a proper target for genetically engineered chimeric antigen receptor T cells (CAR-T cells). Tre...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Background: Actinins are major cytoskeletal proteins that mediate sarcomere function, and they also have important non-muscle functions such as regulating cytokinesis, cell adhesion and migration. There are four isoforms of actinins in mammals (ACTN1-4). Recently, the relationship between actinins and cancer has been discovered in many types of malignancy, yet their prognostic significance in acute myeloid leukemia (AML) remains unclear.Methods: We collected data of 155 de novo AML patients from The Cancer Genome Atlas (TCGA) database; 85 patients received chemotherapy only and 70 patients underwent allogeneic hematopoieti...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
In this study, we generated adriamycin-resistant K562 leukemia (K562/RA) cells and compared the responses of sensitive and resistant leukemia cells to the natural products arsenic trioxide (ATO) and resveratrol (Rsv), with a view to determining whether Rsv potentiates the sensitivity of drug-resistant cells to ATO-induced apoptosis and the associated molecular mechanisms. Our results showed that resistance of K562/RA cells induced by adriamycin treatment was significantly higher (115.81-fold) than that of parental K562 cells. Simultaneously, K562/RA cells were cross-resistant to multiple agents, with the exception of ATO. ...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
CONCLUSIONS: Fenretinide exerts an obvious effect on AML cells both in vitro and in vivo. Besides, the NR4A1-mediated signaling pathway is highly involved in the fenretinide-induced apoptosis of AML cells.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
In this study, we identified the EMT-related gene versican (VCAN) in NPM1-mutated AML across three patient datasets. Further experiments validated the elevated VCAN expression in NPM1-mutated AML primary blasts and OCI-AML3 cells with NPM1 mutation. Mechanistic studies revealed that increased VCAN expression was at least partially regulated by NPM1 mutant via TGF-β/cPML/Smad signalling. Functional evaluations showed that silencing VCAN by shRNA significantly suppressed cell migration and invasion capacity, whereas increased VCAN by overexpressing NPM1-mA enhanced migration and invasion ability of leukemia cells. Final...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Conclusion: Cardiac-specific mortality in AML patients receiving chemotherapy is higher than that in the general population.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
DOCK family proteins are evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase with different cellular functions. It has been demonstrated that DOCK1 had adverse prognostic effect in acute myeloid leukemia (AML). We first analyzed data of 85 AML patients who were treated with chemotherapy and had available DOCK1 to DOCK11 expression information and found that DOCK1 and DOCK2 had prognostic significance in AML. In view of the known prognosis of DOCK1 in AML, we then explored the prognostic role of DOCK2. One hundred fifty-six AML patients with DOCK2 expression data were extracted from The Cancer Genome...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
Future Oncology, Ahead of Print.
Source: Future Oncology - Category: Cancer & Oncology Authors: Source Type: research
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