Screening of high-efficiency and low-toxicity antitumor active components in Macleaya cordata seeds based on the competitive effect of drugs on double targets by a new laminar flow chip
| Autor: | Shumei Wang, Huaidong Peng, Feng Wang, Yue Sun, Jiang Meng, Paul C. H. Li, Hongling Huang, Lisi Li, Yan Gao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Drug
media_common.quotation_subject 02 engineering and technology 01 natural sciences Biochemistry Molecular Docking Simulation Analytical Chemistry chemistry.chemical_compound Electrochemistry Environmental Chemistry Sanguinarine Spectroscopy media_common Macleaya cordata Low toxicity biology 010401 analytical chemistry 021001 nanoscience & nanotechnology biology.organism_classification 0104 chemical sciences Chelerythrine chemistry Toxicity 0210 nano-technology DNA |
| Zdroj: | The Analyst. 146:4934-4944 |
| ISSN: | 1364-5528 0003-2654 |
| Popis: | It is urgent to obtain targeted drugs that selectively bind to pathological targets rather than physiological targets in the early stage of drug screening. G-Quadruplex has become one of the important targets in the development of anti-tumor drugs. However, drugs that target quadruplexes may also bind to dsDNA, which may lead to adverse reactions. In this study, a new three-phase laminar flow chip was constructed to enable the multi-components of a traditional Chinese medicine extract to dynamically and competitively bind with G-quadruplex DNA (on target) and double-stranded DNA (off target), so as to select high-efficiency and low-toxicity anti-tumor drugs. The results showed that there were five compounds in the extracts of Macleaya cordata seeds that exhibited obvious differences in binding to the two targets. Furthermore, the binding constants and modes of four identified alkaloids as they bound to two DNA targets were verified by fluorescence spectra and molecular docking methods. The toxicity to HepG2 and LO2 cells from the four alkaloids was also compared. The results showed that sanguinarine and chelerythrine could be used as candidate drugs with stronger binding to HT24 than DNA26. The chip can also be used for other types of double-target screening of other traditional Chinese medicine extracts or compound libraries. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|