A kind of aryl ruthenium-β-carboline complex and its preparation method and application

Abstract

The invention relates to the field of medicinal chemistry, and specifically discloses an aryl ruthenium-β-carboline complex, a preparation method and application thereof. Described aryl ruthenium-beta-carboline complex is [Ru(η6-arene)(N-N)Cl] (PF6), wherein η6-arene is aryl ligand pair-cymene ( p -cymene, CYM) or benzene (Benzene, Ben), N–N is β-carboline alkaloid derivative 1-(2-pyridine)-9H-pyrido[3,4-b]indole (L1), 1-(2-Quinoline)-9H-pyrido[3,4-b]indole (L2) or 1-(2-imidazole)-9H-pyrido[3,4-b]indole (L3) . The complexes of the present invention exhibit outstanding activity in anti-tumor screening in vitro, and compared with cancer cell lines, their toxicity to normal cells is greatly reduced, and they have good potential for the development of anti-tumor drugs.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, more specifically, to an aryl ruthenium-β-carboline complex and its [0002] Preparation methods and applications. Background technique [0003] One of the characteristics of human malignant tumors is uncontrolled cell cycle regulation. Many molecular targets involved in tumor cell cycle regulation have been discovered, such as cyclin-dependent kinases (CDKs). The cell cycle refers to the whole process through which a cell grows, divides, and proliferates into two cells. The cycle of all eukaryotic cells is tightly controlled into four ordered phases: G1 (pre-DNA synthesis), S (DNA synthesis), G2 (late DNA synthesis), and M (mitosis). To make cells pass through each cycle correctly, the key depends on different mitogenic signals from the surrounding cells, including Cyclin, cyclin-dependent kinases and CDK inhibitors (Cyclin-dependent kinase inhibitors, CKIs). At least 13 CDKs are currently ...

AI Technical Summary

Problems solved by technology

[0005] Representative of metal-based antineoplastic drugs—platinum-based drugs have made remarkable achievements (currently 6 platinum-based drugs are on the market worldwide), but they still cannot fully solve many of the shortcomings similar to cisplatin, such as their effects on a variety of tumors. Doesn't work and usually causes serious side effects such as nausea, bone marrow suppression, and nephrotoxicity

Since the toxic and side effects of platinum-based drugs severely limit their practical efficacy and scope of application, it is a current research hotspot to find new metal-based anticancer drugs with different mechanisms of action to improve or supplement the performance of existing platinum-based drugs.

Since traditional metal anti-tumor drugs mostly target double-stranded DNA, it is difficult to break through the limitations of platinum-based drugs. New metal complex anti-tumor drugs designed for tumor-specific molecules may go beyond the clinical Platinum metal antineoplastic drugs

Most of the small molecule inhibitors of CDKs in clinical and preclinical studies are organic compounds, and metal complexes are relatively lacking as CDKs inhibitors

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