Design, synthesis, and biological evaluation of harmine derivatives as topoisomerase I inhibitors for cancer treatment.

A series of ß-carboline derivatives were designed and synthesized by introducing the chalcone moiety into the harmine. The synthesized derivatives were evaluated their anti-proliferative activities against six human cancer cell lines (MCF-7, MDA-MB-231, HepG2, HT29, A549, and PC-3) and one normal cell line (L02). Among them, compound G11 exhibited the potent anti-proliferative activity against MCF-7 cell line, with an IC50 value of 0.34 µM. Further biological studies revealed that compound G11 inhibited colony formation of MCF-7 cells, suppressed MCF-7 cell migration by downregulating migration-associated protein MMP-2. In addition, it could induce apoptosis of MCF-7 cells by downregulating Bcl-2 and upregulating Cleaved-PARP, Bax, and phosphorylated Bim proteins. Furthermore, compound G11 can act as a Topo I inhibitor, affecting DNA synthesis and transcription, thereby inhibiting cancer cell proliferation. Moreover, compound G11 inhibited tumor growth in 4T1 syngeneic transplant mice with an inhibition rate of 43.19 % at a dose of 10 mg/kg, and 63.87 % at 20 mg/kg, without causing significant toxicity to the mice or their organs, achieving the goal of reduced toxicity and increased efficacy. All these results indicate of G11 has enormous potential as an anti-tumor agent and merits further investigation.

Fluorescence "Off-On" Probe for L-Cysteine Detection Based on Nitrogen Doped Carbon Dots.

Herein, a simple and efficient fluorescence analysis method for L-Cysteine (L-Cys) was established. The method was based on the fluorescent "off-on" mode of nitrogen doped carbon dots (NCDs). The NCDs were prepared via a facile one-step solvothermal method. In the process of exploring the bio-functional application of these newly synthesized NCDs, we found these NCDs with rich functional groups exhibited excellent optical properties. In addition, these newly synthesized NCDs showed an excitation-dependent emissions photolumine-scent (PL) property and exhibited good performance in the detection of Fe3+ ions by quenching the blue emission fluorescence. Interestingly, the quenched fluorescence of NCDs was recovered with the addition of L-Cys, which provided a novel approach for L-Cys detection. The NCDs-based fluorescent "off-on" sensor has a wide linear detection range (0-100 µM), and a relatively low detection limits (0.35 µM) for L-Cys. This simple fluorescent "off-on" approach is, very sensitive and selective for L-Cys detection, which also provides a new insight on NCDs biosensor application.