CN-122011052-A - Iridium-kaempferol complex, preparation method and application thereof

Abstract

The invention relates to the technical field of medicines, in particular to an iridium-kaempferol complex, a preparation method and application thereof. According to the invention, an Ir (Cp) Cl 2 structure in [ Ir (Cp) Cl 2 ] 2 is replaced by 1C 15 H 10 O 6 to prepare the iridium-kaempferol complex, the center of Ir (III) is combined with a kaempferol ligand for the first time, and a metal organic complex Ir-Kae which not only utilizes the stability of the Ir (III) complex, but also utilizes the pharmacological activity of kaempferol is developed, and the effective treatment of spinal cord injury by multiple targets can be realized through the synergistic action of multiple mechanisms such as antioxidation, anti-inflammatory and neuroprotection. The Ir-Kae has remarkable free radical scavenging capability, can effectively reduce the active oxygen level in cells and organisms thereof, realizes remarkable oxidation resistance and oxidation stress resistance, can improve the living degree of injured hippocampal neurons, promotes neuron repair, effectively treats nerve injury and spinal cord injury thereof, and provides a new direction for spinal cord injury drug auxiliary treatment.

Inventors

• MA YANMING
• LIU SHENGHANG
• ZHAO YUQI
• HU HUIMIN
• ZHU LEI
• JU CHENG
• LUO RONGJIN

Assignees

• 西安市红会医院（西安市骨科研究所）

Dates

Publication Date

20260512

Application Date

20260127

Claims (10)

1. 1. The iridium-kaempferol complex is characterized by having the following structural formula: 。
2. 2. the method for preparing the iridium-kaempferol complex as claimed in claim 1, which is characterized by comprising the following steps: S1, dissolving [ Ir (Cp×) Cl 2 ] 2 and kaempferol in an alcohol solvent of C1-C4, adjusting the pH of the solution to 8-14, and reacting at 60-80 ℃ for not less than 1h; and S2, after the reaction is finished, removing the solvent, and purifying the residue.
3. 3. The method for producing iridium-kaempferol complex according to claim 2, wherein the molar ratio of [ Ir (cp×) Cl 2 ] 2 to kaempferol in step S1 is (2-3): 4-6.
4. 4. The method for producing an iridium-kaempferol complex according to claim 2, wherein the reaction is performed under heating after the pH of the solution is adjusted to 10 in step S1.
5. 5. The method for preparing iridium-kaempferol complex as claimed in claim 2, wherein, The residue was purified by silica gel column chromatography in step S2.
6. 6. The iridium-kaempferol complex as claimed in claim 1 or the iridium-kaempferol complex prepared by the preparation method of any one of claims 2 to 6, and the application of the iridium-kaempferol complex in preparing medicaments for preventing and/or treating oxidative stress related diseases.
7. 7. The use of claim 6, wherein the oxidative stress-related disease comprises a nerve injury-related disease comprising a secondary spinal cord injury.
8. 8. The use according to claim 6 or 7, wherein the iridium-kaempferol complex in the medicament is the only active ingredient.
9. 9. A medicament for the treatment and/or adjuvant treatment of a disease associated with nerve damage, comprising an effective amount of an iridium-kaempferol complex as claimed in claim 1 and a pharmaceutically acceptable adjuvant.
10. 10. A medicament for the treatment and/or adjuvant treatment of a disease associated with nerve damage according to claim 9, wherein the iridium-kaempferol complex is the only active ingredient.

Description

Iridium-kaempferol complex, preparation method and application thereof Technical Field The invention relates to the technical field of medicines, in particular to an iridium-kaempferol complex, a preparation method and application thereof. Background Spinal cord injury (Spinal Cord Injury, SCI) is a severe traumatic disorder of the central nervous system, which refers to a pathological condition in which spinal cord tissue changes its structure and function due to external mechanical forces, thereby causing temporary or permanent loss of motor, sensory and autonomic nerve functions below the plane of injury. In pathophysiology, the progression of spinal cord injury can be divided into two phases, primary injury and secondary injury. The primary injury is caused by external force directly acting on the spine and spinal cord, and is often accompanied by mechanical damage such as vertebral fracture, dislocation, disc herniation and the like, so that the spinal cord tissue is instantaneously cracked, bleeding or pressed. The subsequent initiation of secondary injury is a complex series of cell and molecule cascades including ischemia, inflammatory reactions, ion imbalances, lipid peroxidation, and apoptosis, which further expands the extent and severity of spinal cord injury. Studies have shown that oxidative stress related signaling pathways such as MAPK, NF- κ B, HIF-1, etc. are significantly activated after SCI, the mechanism of action is closely related to cellular responses to hypoxia, reactive oxygen metabolic processes and regulation of neuronal death. Therefore, effective scavenging of a large number of oxygen radicals generated in the acute stage of SCI, or inhibition of its overproduction, remodeling of redox balance, has become an important therapeutic strategy for blocking the progress of secondary injury and promoting nerve repair. In the field of pharmaceutical development, metal complexes are of interest because of their unique electronic structure and controllable chemical properties. Among them, iridium (III) (Ir (III)) complexes have been widely studied in the fields of chemical sensors, biological probes, photocatalysis, organic light emitting diodes, and the like, due to their high emission efficiency, long excited state lifetime, excellent photo-thermal stability, and easy tunability of emission wavelength. In recent years, some Ir (III) complexes have also been explored for biomedical applications. However, the mechanism of action of Ir (III) complexes reported in the prior art in the treatment of diseases is mainly focused on the generation of Reactive Oxygen Species (ROS) by utilizing their photophysical properties. For example, various cationic Ir (III) complexes have been reported for photodynamic therapy (PDT) or chemodynamic therapy (CDT), which act as photosensitizers or catalysts to promote ROS production to kill tumor cells. This "pro-oxidative" strategy is diametrically opposed to the "antioxidant" strategy required to treat oxidative stress-related diseases. On the other hand, natural small molecular compounds are an important source for drug discovery, and kaempferol (Kaempferol) is a naturally occurring flavonoid compound which is widely existing in various fruits, vegetables and Chinese herbal medicines. Research shows that kaempferol has various pharmacological activities including antioxidation, anti-inflammatory and antibacterial. The antioxidant activity is derived from phenolic hydroxyl groups in the structure, and can directly remove free radicals or activate endogenous antioxidant channels (such as Nrf2 channels). However, kaempferol has the limitations of low bioavailability, fast in vivo metabolism, relatively dispersed acting targets and the like as a single component, and limits the exertion of clinical curative effects. In summary, the development of a technical scheme of a metal organic complex capable of resisting oxidative stress to treat spinal cord injury by combining the stability and the easy modification of an Ir (III) complex with the definite antioxidant activity of kaempferol is very significant. However, no report is known. Disclosure of Invention Therefore, based on the background, the iridium-kaempferol complex, the preparation method and the application thereof are provided, the iridium (III) center and the kaempferol ligand are combined for the first time, and the iridium-kaempferol complex Ir-Kae which can not only utilize the stability of the Ir (III) complex, but also utilize the multi-target pharmacological activity of kaempferol is developed, and can realize the multi-mechanism synergistic treatment of spinal cord injury by inhibiting oxidative stress, regulating and controlling inflammatory microenvironment and promoting the recovery of nerve functions, thereby providing a new direction for the drug treatment of spinal cord injury. The technical scheme provided by the invention is as follows: The iridium-kaempferol complex has the following s