No abstract

Excessive aluminum exposure in the human body has been held responsible for multiple adverse effects, and existing data underscore the significance of aluminum detection in environmental and biological systems. Developing high‐performance Al3+ fluorescent chemosensors can revolutionize our understanding of the physiological and pathological processes of Al3+ ions. Herein, we reported a highly sensitive and selective Schiff base fluorescence sensor, bis‐NAPPD (1,1'‐((1E,1'E)‐(pyridine‐2,3‐diylbis(azanylylidene))bis(methanylylidene))bis(naphthalen‐2‐ol)), which can recognize Al3+ ions and exhibits a remarkable turn‐on dual emission response (by ~23 fold) with a low nanomolar level detection limit (1.67 × 10−8 M) in methanol. Furthermore, the binding behavior and the turn‐on fluorescence probing mechanism of bis‐NAPPD were illustrated in detail by UV–vis titration, 1H NMR, and ESI‐MS spectroscopy as well as density functional theory calculations. Notably, bis‐NAPPD showed great potential for tracing Al3+ distribution in cells and living zebrafish larvae, and can also be applied in the fluorimetric detection of aluminum in sucralfate tablets with good precision and satisfactory accuracy, which may represent a promising Al3+ probe in bioimaging and biomedical applications.

Two platinum Pol I selective inhibitors P1-Q1 and P1-Q2 target the Pol I transcription machinery, facilitate the formation and stabilization of R-loops, induce severe DNA damage, and display synthetic lethality in BRCA1-deficient A549 cells.

Twenty‐two quaternary 8‐dichloromethylprotoberberine alkaloids were synthesized from unmodified quaternary protoberberine alkaloids (QPAs) to improve their physical and chemical properties and to obtain selectively anticancer derivatives. The synthesized derivatives showed more appropriate octanol/water partition coefficients by up to values 3–4 compared to unmodified QPA substrates. In addition, these compounds exhibited significant antiproliferative activity against colorectal cancer cells and lower toxicity on normal cells, resulting in more significant selectivity indices than unmodified QPA compounds in vitro. The IC50 values of antiproliferative activity of quaternary 8‐dichloromethyl‐pseudoberberine 4‐chlorobenzenesulfonate and quaternary 8‐dichloromethyl‐pseudopalmatine methanesulfonate against colorectal cancer cells are 0.31 μM and 0.41 μM, respectively, significantly stronger than those of other compounds and positive control 5‐fluorouracil. These findings suggest that 8‐dichloromethylation can be used as one of the modification strategies to guide the structural modification and subsequent investigation of anticancer drugs for CRC based on QPAs.

Natural QPAs have anti-cancer property. The prodrugs of QPAs synthesized in our work with significantly improved solubility showed significantly stronger activity in animal experiments. Nevertheless, the mechanism of action of QPAs for treating cancers remains poorly understood. Here, a chemoproteomic study reveals that QPAs non-covalently and multivalently bind to PES1 in CRC cells, which impinges on the direct interaction between hTERT and hTR in the assembly of the telomerase complex, downregulates telomerase activity, and so promotes the aging process of CRC cells. This study is beneficial for us to conduct extensively the pharmaceutical chemistry research of QPAs.