Design and Synthesis of Thiourea-Conjugating Organic Arsenic D-Glucose with Anticancer Activities.

Organic arsenic compounds such as p-aminophenylarsine oxide (p-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic properties, therapeutic efficacy, and target selectivity. In order to strengthen the selectivity of 4-(1,3,2-dithiarsinan-2-yl) aniline 7 to tumor cell, a thiourea moiety was used to strengthen the anticancer activity. To avoid forming a mixture of α/ß anomers, the strategy of 2-acetyl's neighboring group participation was used to lock the configuration of 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate from 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide. 1-(4-(1,3,2-dithiarsinan-2-yl) aniline)-2-N-(2,3,4,6-tetra-O-acetyl-ß-d-glucopyranos-1-yl)-thiourea 2 can increase the selectivity of human colon cancer cells HCT-116 (0.82 ± 0.06 µM vs. 1.82 ± 0.07 µM) to human embryonic kidney 293T cells (1.38 ± 0.01 µM vs. 1.22 ± 0.06 µM) from 0.67 to 1.68, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.

Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer.

Cell-free RNA (cfRNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cfRNA isolation technologies due to the low abundance and instability of cfRNA. Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids (containing cfRNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework (MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cfRNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cfRNA in serum from patients with liver cancer was described and a cfRNA signature with six cfRNAs was identified to diagnose liver cancer with high diagnostic efficiency (area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.