Fluorescent drugs and pyrimidine-indole scaffolds have been shown to have advantages in cancer treatment. Fluorescent antitumor drugs BF 3 - o, m, p- phenylenediamine pyrimidine-indole derivatives (PYB1, PYB2, and PYB3) were synthesized by linking pyrimidine and indole groups with aniline through a simple step and introducing BF 3 . The drugs exhibit promising antitumor activity and their fluorescent properties make them useful for imaging purposes. The optical properties of the three compounds have been investigated. All of them have fluorescent properties and compound PYB2 has good fluorescent properties. Additionally, the in vitro cytotoxicity of these compounds was evaluated against the human cancer cell line HeLa and the human normal cell line L02. The inhibition rates of HeLa cells treated with PYB1, PYB2, and PYB3 at a concentration of 19.2 μg/mL were 80.91%, 77.72%, and 65.94%, respectively. These results indicate a strong inhibitory effect on cancer cells. Further through the cell imaging experiment, we can see that PYB2 can enter the cell through the cell membrane through the fluorescence scattering diagram, which has good biocompatibility. In addition, the possible interactions between the compounds and Ras protein active sites were analyzed by molecular docking. The three compounds can bind well to Ras protein through hydrogen bonding. This study provides a basis for the development and modification of pyrimidine-indole fluorescent anticancer drugs. Compound PYB2 shows potential as a fluorescent anticancer drug. Graphical abstract
Elucidation of the pathway of drug delivery and carrier degradation in vivo is essential for the fabrication of a feasible drug delivery system. Multispectral fluorescence imaging can track a drug delivery system simultaneously based on the separation of fluorescence at multiple wavelengths without interference. In this study, the Doxorubicin loaded genipin-crosslinked globin and PEI nanoparticles (Gb-G-PEI/Dox NPs) were designed as a dual fluorescent drug delivery system to track the drug release and carrier degradation process. Both confocal laser scanning microscopy and flow cytometric results showed that Gb-G-PEI/Dox NPs had a higher cellular uptake efficiency than Doxorubicin in the Bel-7402 cell line due to its small size and positively charged surface. The in vivo metabolism experiments tracked by the multispectral fluorescence imaging system elucidated the sustained drug release and carrier degradation process of the Gb-G-PEI/Dox NPs. Furthermore, the in vivo antitumor effects study by the bioluminescence imaging showed that Gb-G-PEI/Dox NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. As a result, Gb-G-PEI/Dox NPs were demonstrated to be a highly efficient, feasible and visible drug delivery system for tumor therapy.
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