A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency.

In this work, a series of diaryl benzo[b][1,4]thiazepine derivatives D1-D36 were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. They were designed by introducing the seven-member ring benzothiazepine as the linker for CA-4 modification for the first time. Among them, the hit compound D8 showed potential on inhibiting the growth of several cancer cell lines (IC50 values: 1.48 µM for HeLa, 1.47 µM for MCF-7, 1.52 µM for HT29 and 1.94 µM for A549), being comparable with the positive controls Colchicine and CA-4P. The calculated IC50 value of D8 as an tubulin polymerization inhibitor was 1.20 µM. The results of the flow cytometry assay revealed that D8 could induce the mitotic catastrophe and the death of living cancer cells. D8 also indicated the anti-vascular activity. The possible binding pattern was implied by docking simulation, inferring the possibility of introducing interactions with the nearby tubulin chain. Since the novel structural trial has been conducted with preliminary discussion, this work might stimulate new ideas in further modification of tubulin-related anti-cancer agents and therapeutic approaches.

An umbelliferone-derivated fluorescent sensor for selective detection of palladium(II) from palladium(0) in living cells.

Palladium (Pd) has drawn worldwide attentions because its connections to industry, chemistry, biological material and public health. Quantitative and selective detection tools for Pd and its ion forms are in urgent necessity. Here an umbelliferone derivative Umb-Pd2 was provided as a small, steady, safe and selective sensor for detecting Pd(II). It indicated advantages including sensitive (LOD 1.1 nM), wide pH tolerance (5.0-10.0), applicable linear range (0-1.8 equivalent) and low toxicity. The most attractive point was its explicit selectivity towards Pd(II) from Pd(0) in both independent and coexistence systems. This distinguishing ability was further utilized in imaging in living cells, raising this work as a rare and important example among all the published papers on palladium sensing. Thus, Umb-Pd2 supplied a potential approach for further improvement and applications in both daily chemistry and public health.

A rapid cell-permeating turn-on probe for sensitive and selective detection of sulfite in living cells.

A rapid cell-permeating probe NJUXJ-1 was introduced for sensitive and selective detection of sulfite in living cells. It generated a turn-on response to sulfite with high sensitivity (detection limit 13.0 nM) and selectivity (at a physiological level) and low toxicity. The fluorescence of the detecting system was steady for a wide pH range (5-8) and a long period of time (over 12 h). The most attractive point, its rapid cell-permeating ability, made it suitable for bioimaging with a 2 min incubation time and shortened the whole detecting period (cell-permeation and reaction), and thus could decrease background interference. It offered a convenient approach for determining exogenous or endogenous sulfite levels in living cells and further applications.

A new selective fluorescence probe with a quinoxalinone structure (QP-1) for cysteine and its application in live-cell imaging.

A new selective probe with a quinoxalinone structure, QP-1, has been developed for detection of Cys from biothiols. QP-1 features superb selectivity to Cys and a wide pH range. QP-1 has selectivity to Cys over Hcy, GSH, other amino acids and ions. HRMS spectra confirmed that the detection process was a conjugate addition-addition-elimination reaction. Moreover, QP-1 has been successfully applied in the imaging of Cys in living cells. Finally, QP-1 has been used to detect Cys in rat urine samples.