CN-121648133-B - Application of small molecular compound of targeted phosphorylated ARMC 10S 43 in preparation of drugs for treating nervous system injury caused by tin exposure

Abstract

The invention relates to the technical field of heavy metal exposure related disease treatment medicines, in particular to application of a small molecular compound of a targeted phosphorylated ARMC10 serine 43 site in preparation of a medicine for treating nervous system injury caused by tin exposure. According to the technical scheme, the abnormal phosphorylation of ARMC10 can be specifically induced by the exposure of trimethyltin chloride for the first time, so that neuronal death and cognitive impairment are induced. Based on the mechanism, a small molecular compound targeting the specific phosphorylation site of ARMC10 is provided, and the nerve injury is effectively reversed by blocking the abnormal division and dysfunction of mitochondria mediated by the small molecular compound, so that the structure and the function of neurons are protected. The scheme solves the problem that the tin exposure related nervous system injury has no effective therapeutic drug due to the lack of a definite drug target point in the prior art, and has ideal application prospect. The small molecular compound has the advantages of clear structure, clear action mechanism, easy subsequent development, good drug property and good commercialization prospect.

Inventors

• Pi Huifeng
• YU ZHENGPING
• DENG PING
• Qin Mingke
• YANG LINGLING
• XIE JIA
• JIE CHENG
• HE MINDI
• GAO PENG
• ZHOU ZHOU

Assignees

• 中国人民解放军陆军军医大学

Dates

Publication Date

20260505

Application Date

20260202

Claims (3)

1. 1. The application of the small molecular compound in preparing the medicine for treating the nervous system injury caused by tin exposure is characterized in that the structural formula of the small molecular compound is shown as formula II or formula V: A formula II; Formula V.
2. 2. The use of a small molecule compound according to claim 1 for the manufacture of a medicament for the treatment of nervous system injury caused by tin exposure, wherein the nervous system injury caused by tin exposure is acute/subacute nervous system injury caused by organotin exposure.
3. 3. Use of a small molecule compound according to claim 2 for the manufacture of a medicament for the treatment of neurological damage caused by tin exposure, characterized in that: the organic tin is trimethyltin chloride.

Description

Application of small molecular compound of targeted phosphorylated ARMC 10S 43 in preparation of drugs for treating nervous system injury caused by tin exposure Technical Field The invention relates to the technical field of heavy metal exposure related disease treatment medicines, in particular to application of a small molecular compound of targeted phosphorylated ARMC 10S 43 in preparation of a medicine for treating nervous system injury caused by tin exposure. Background In the background of increasing environmental health risks, the dual threat of toxic pollutants to ecology and human health has become a focus of international social concern. Trimethyltin chloride (TRIMETHYLTIN CHLORIDE, TMT) has been widely used as a typical class of organotin compounds. Despite their limited use, the use of these materials in industrial processes such as PVC plastic processing is still not entirely avoided in some areas with the occurrence of toxic patients each year. TMT is still often contaminated by various means such as waste water discharge, processed products, etc., and is frequently detected not only in drinking water, foods, daily chemical products, but also in human tissues, thus constituting an exposure risk. Numerous studies have shown that TMT has significant neurotoxicity, especially in the targeted hippocampus to trigger cognitive dysfunction. The toxic effect is closely related to mitochondrial injury, and TMT exposure can induce excessive Reactive Oxygen Species (ROS) to generate and disturb intracellular calcium homeostasis, thereby destroying mitochondrial structural integrity and respiratory chain function. In recent years, studies have further revealed that mitochondrial dynamics imbalance (deregulation of fusion and division processes) is the core pathological mechanism of TMT-induced neuronal dysfunction. For example, TMT can lead to swelling, vacuolation and reduced numbers of hippocampal neurons in mitochondria, while interventions such as artemisinin effectively alleviate neuronal apoptosis and improve behavioral defects by restoring mitochondrial morphology and content, highlighting the potential of targeted mitochondrial dynamic regulation in neuroprotection. In this context, ARMC10 (arma-containing repeat protein 10) was gradually demonstrated to be a key factor in regulating mitochondrial dynamics as a newly identified mitochondrial outer membrane protein. ARMC10 can dynamically modulate its activity through post-translational modifications (e.g., phosphorylation), which in turn affect mitochondrial morphology, energy metabolism, and neuronal survival. However, a key gap remains, and it is not clear whether ARMC10 is involved in TMT-induced mitochondrial dysfunction and its downstream neurotoxicity processes, nor is there evidence that it can serve as a molecular target for antagonizing organotin neurotoxicity. Specifically, whether TMT exposure affects the expression, localization, or modification status of ARMC 10. Whether the functional change of ARMC10 is sufficient to determine the sensitivity of neurons to TMT toxicity. None of these problems were solved by the system. As such, the lack of mechanism resolution and intervention strategies based on the ARMC10 pathway has become a major technical bottleneck in the development of targeted neuroprotective therapies. Disclosure of Invention The invention aims to provide an application of a small molecular compound of targeted phosphorylated ARMC 10S 43 in preparing a medicament for treating nervous system injury caused by tin exposure, so as to solve the technical problem that no effective therapeutic medicament exists for treating the nervous system injury related to tin exposure due to the lack of a definite medicament target spot in the prior art. In order to achieve the above purpose, the invention adopts the following technical scheme: the application of a small molecular compound in preparing a medicament for treating nervous system injury caused by tin exposure is provided, wherein the structural formula of the small molecular compound is shown as formula II or formula V: A formula II; Formula V. Further, small molecule compounds of formula II or formula V are useful for targeting ARMC10 proteins with serine at position 43 phosphorylated. Further, the affinity of the small molecular compound shown in the structural formula II to the ARMC10 protein phosphorylated by serine at position 43 is-9.783 kcal/mol, and the affinity of the small molecular compound shown in the structural formula V to the ARMC10 protein phosphorylated by serine at position 43 is-9.291 kcal/mol. Further, tin exposure results in nervous system injury as acute/subacute nervous system injury resulting from organotin exposure. Further, the organotin is trimethyltin chloride. Further, the damage to the nervous system is manifested by reduced neuronal activity, impaired neuronal mitochondrial function, and abnormal morphology of neuronal mitochondria. Further, the st