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Ursolic acid (UA) is a natural product which has been shown to possess a wide range of pharmacological activities, in particular those with anticancer activity. In this study, 13 novel ursolic acid derivatives were designed and synthesized in an attempt to further improve compound potency. The structures of the newly synthesized compounds were confirmed using mass spectrometry, infrared spectroscopy, and (1) H NMR. The ability of the UA derivatives to inhibit cell growth was assayed against both various tumor cell lines and a non-pathogenic cell line, HELF. Analysis of theoretical toxicity risks for all derivatives was performed using OSIRIS and indicated that the majority of compounds would present moderate to low risks. Pharmacological results indicated that the majority of the derivatives were more potent growth inhibitors than UA. In particular, 5b demonstrated IC50 values ranging from 4.09 ± 0.27 to 7.78 ± 0.43 μm against 12 different tumor cell lines. Flow cytometry analysis indicated that 5b induced G0/G1 arrest in three of these cell lines. These results were validated by structural docking studies, which confirmed that UA could bind to cyclins D1 (Cyc D1) and cyclin-dependent kinases (CDK6), the key regulators of G0/G1 transition in cell cycle, while the piperazine moiety of 5b could bind with glucokinase (GK), glucose transporter 1 (GLUT1), and ATPase, which are the main proteins involved in cancer cell metabolism. Acridine orange/ethidium bromide staining confirmed that 5b was capable of inducing apoptosis and decreasing cell viability in a dose-dependent manner.

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Irreversible organ damage or even death frequently occurs when humans or animals unconsciously drink contaminated water. Therefore, in many countries drinking water is disinfected to ensure harmful pathogens are removed from drinking water. If upstream water treatment prior to disinfection is not adequate, disinfection by-products (DBPs) can be formed. DBPs can exist as wide variety of compounds, but up till now, only several typical compounds have drinking water standards attributed to them. However, it is apparent that the range of DBPs present in water can comprise of hundreds of compounds, some of which are at high enough concentrations that can be toxic or potentially carcinogenic. Hence, it becomes increasingly significant and urgent to develop an accessible, affordable and durable sensing platform for a broader range and more sensitive detection of DBPs. Compared with well-established laboratory detection techniques, electrochemical sensing has been identified as a promising alternative that will provide rapid, affordable and sensitive DBPs monitoring in remote water sources. Therefore, this article provides a review on current state-of-the-art development (within last decade) in electrochemical sensing to detect organic DBPs in water, which covered three major aspects: (1) recognition mechanism, (2) electrodes with signal amplification, and (3) signal read-out techniques. Moreover, comprehensive quality assessments on electrochemical biosensors, including linear detection range, limit of detection (LoD) and recovery, have also been summarized.

Graphene exhibits excellent physical, electronic and chemical properties that are highly desirable for biosensing application. However, most graphene biosensors are based on graphene lying flat on a substrate and therefore not utilizing its maximum specific surface area for ultra-sensitive detection. Herein, we showcased the novel use of photonic annealing on flexographic printed graphene-ethyl cellulose composite to produce vertically aligned graphene (VAG) biosensors for ultra-sensitive detection of algal toxin in drinking water. These VAG structures, which maximized the specific surface area of graphene, were formed by partial removal of the polymeric binder upon applying the intense pulsed light on the printed graphene. A label-free and low-cost VAG biosensor based on non-faradaic electrochemical impedance spectroscopy technique was fabricated. The biosensor exhibited a limit of detection (LoD) of 1.2 ng/L for MC-LR in local tap water. Such ultra-sensitive VAG biosensor is suitable for low-cost mass production using an integrated roll-to-roll flexographic printing with rapid photonic annealing technique.