Vinburnine

Vinburnine (VNB) is a vinca alkaloid used as a vasodilator to enhance cerebral circulatory insufficiency. It is a cyclic amide containing drug which is expected to be sensitive to hydrolytic degradation. The degradation profile of VNB was studied in this work following ICH recommendations for stability study. The drug was sensitive only to degradation with NaOH with the formation of the carboxylic acid derivative, identified by IR and ¹H NMR analyses as 2-((1S,12bS)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizin-1-yl) acetic acid, (DEG). In this study five simple, smart and univariate stability indicating spectrophotometric methods were developed and validated for simultaneous determination of VNB and DEG for the first time. The developed methods include; Dual Wavelength Method (DWM), Dual Wavelength Resolution Method (DWRM), Factorized Absorbance Difference Method (FADM), Advanced Absorbance Subtraction Method (AASM), and Derivative Amplitude Factor Method (DAFM). These methods were capable of determination of VNB and DEG over the ranges of 1-30 and 3-50 µg/mL, respectively. The proposed methods were simple, smart, specific, and could be applied for analyzing synthetic mixtures of VNB and DEG and were successfully applied for determination of the drug in commercially available capsules. The obtained results of these methods were statistically compared with the reported HPLC one using student's-t and F- tests, where no significant difference was observed. Validation of the developed methods was applied according to ICH recommendations and all the results were within the acceptable limits.

Objective: Our current study is to explore the prognostic value and molecular mechanisms underlying the role of lncRNA in non-homologous end joining pathway 1 (LINP1) in early stage pancreatic ductal adenocarcinoma (PDAC). Methods: Genome-wide RNA-seq datasets of 112 early stage PDAC patients were got from The Cancer Genome Atlas and analyzed using multiple online tools. Results: Overall survival in high LINP1 expression patients was shorter than those with low expression (high-LINP1 vs. low-LINP1=481 vs. 592 days, log-rank P=0.0432). The multivariate Cox proportional hazard regression model suggested that high-LINP1 patients had a markedly higher risk of death than low-LINP1 patients (adjusted P=0.004, hazard ratio=2.214, 95% confidence interval=1.283-3.820). Analysis of genome-wide co-expressed genes, screening of differentially expressed genes, and gene set enrichment analysis indicated that LINP1 may be involved in the regulation of cell proliferation-, cell adhesion- and cell cycle-related biological processes in PDAC. Six small-molecule compounds including STOCK1N-35874, fenofibrate, exisulind, NU-1025, vinburnine, and doxylamine were identified as potential LINP1-targeted drugs for the treatment of PDAC. Conclusions: Our study indicated that LINP1 may serve as a prognostic biomarker of early stage PDAC. Analysis of genome-wide datasets led to the elucidation of the underlying mechanisms and identified six potential targeted drugs for the treatment of early PDAC.