CN-121974956-A - Beta-diketone iridium complex and preparation method and application thereof

Abstract

The invention particularly discloses a beta-diketone iridium complex, a preparation method and application thereof, and relates to the technical field of biological medicine. The beta-diketo iridium complex provided by the invention has high phototoxicity and low dark toxicity, can be used as an effective PSs of PDT (PDT) to be applied to tumor cells, and is specifically delivered to the tumor cells by taking a traditional Chinese medicine monomer tripterine as a supplement and combining with a nano targeting delivery technology, so that the beta-diketo iridium complex is used for photodynamic/immune cooperative treatment of hypoxic tumors.

Inventors

• LI ZHENBAO
• FENG ZHIHUI
• LIU XUAN
• HUANG PENG
• WANG YUAN
• LI BAOMING
• JI JUNQIU
• WANG DIANLEI
• CHENG ZHIFEI

Assignees

• 安徽中医药大学

Dates

Publication Date

20260505

Application Date

20260318

Claims (10)

1. 1. The beta-diketone iridium complex is characterized by having a structure shown in a formula (I); Formula (I).
2. 2. The β -diketiminate iridium complex according to claim 1, further comprising pharmaceutically acceptable salts, esters, hydrates, solvates, metabolites, prodrugs, stereoisomers, tautomers, polymorphs and/or isotopic derivatives thereof.
3. 3. A process for the preparation of a β -diketiminate iridium complex as claimed in claim 1 or claim 2, comprising: s1, reacting 3-ethoxy-4-hydroxybenzaldehyde with o-amino thiophenol to obtain L1; S2, reacting L1 with bromooctane to obtain L2; s3, reacting L2 with iridium trichloride trihydrate to obtain M; S4, reacting M with acetylacetone to obtain the beta-diketone iridium complex.
4. 4. A β -diketone iridium complex, which is obtained by the production method according to claim 3.
5. 5. A nanoparticle comprising a phospholipid, tripterine and the β -diketone iridium complex of claim 1 or 2 or 4.
6. 6. The nanoparticle according to claim 5, wherein the mass ratio of the phospholipid, the tripterine and the beta-diketone iridium complex is 4 (0.1-5): 0.1-5.
7. 7. A pharmaceutical composition, in the form of a capsule, characterized by comprising the following steps: (1) A therapeutically effective amount of a β -diketiminate iridium complex as claimed in claim 1 or 2 or 4 and/or a nanoparticle as claimed in claim 5 or 6; (2) Pharmaceutically or immunologically acceptable carriers or excipients.
8. 8. A pharmaceutical formulation comprising the pharmaceutical composition of claim 7.
9. 9. A pharmaceutical product comprising the pharmaceutical formulation of claim 8.
10. 10. Use of a β -diketiminate iridium complex according to claim 1 or 2 or 4, a nanoparticle according to claim 5 or 6, a pharmaceutical composition according to claim 7, a pharmaceutical formulation according to claim 8 and/or a pharmaceutical product according to claim 9 for the manufacture of a medicament for the prophylaxis and/or treatment of breast cancer.

Description

Beta-diketone iridium complex and preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a beta-diketone iridium complex and a preparation method and application thereof. Background Cancer is a malignant disease that severely threatens human health, with high morbidity and mortality. Aiming at the common methods of cancer treatment, such as chemotherapy, radiotherapy, immunotherapy and photodynamic therapy (PDT), PDT has been paid attention to in recent years due to the advantages of non-invasiveness, high specificity, strong controllability, small side effects and the like. PDT is based on photochemotherapeutic strategies, consisting mainly of three elements, light, photosensitizers (PSs) and oxygen (O 2), of which the largest research space is the PSs. PSs are capable of photocatalytically generating harmful Reactive Oxygen Species (ROS) under photoactivation, including superoxide radicals (O 2. Cndot. -), hydroxyl radicals (. OH) and hydrogen peroxide (H 2O2) generated by electron transfer (type I), and singlet oxygen (1O 2) generated by energy transfer (type II), causing oxidative damage to surrounding tissues, presenting a localized tumor treatment. Currently, the developed PSs have many problems such as complicated material synthesis routes, difficulty in purification, poor stability, and easiness in self-aggregation under physiological conditions and reduction of fluorescence intensity. Traditional Chinese medicine often emphasizes strengthening body resistance to eliminate pathogenic factors in treating tumor diseases, and utilizes the vital qi to eliminate the struggle between pathogenic factors, which is the best of the same worker as immunotherapy. Immunotherapy is also often used in combination with chemotherapeutic drugs in clinical applications, with the aim of strengthening body resistance while enhancing the efficacy of eliminating pathogens. Modern pharmacology also proves that many Chinese medicaments such as ginseng, astragalus and the like which can tonify and strengthen body resistance can improve the immune system and promote healthy energy. The natural compound extracted from the traditional Chinese medicine has potential clinical application value, low toxicity and high efficiency, and can be used for breaking through the existing bottleneck of the traditional anticancer therapy. Tripterine (Cel) is pentacyclic triterpene component extracted from radix Tripterygii Wilfordii root bark, and has anti-inflammatory and antitumor effects, and has anticancer activity on tumor cells such as breast cancer, hepatocarcinoma, melanoma, glioma, etc. Huang Lifu teaches that Cel has dual immunoregulatory effects by recruiting cytotoxic CD8 + T cells and NK cells to the tumor immune microenvironment to induce ICD on the one hand, and by directly activating T cells by downregulating PD-L1 expression of tumor cells on the other hand, to achieve immunosuppressive TME remodeling. Recently, from the professor team's Cel as a multifunctional copper ionophore, a self-amplified copper death nanoparticle (Cel-cu@NPs) was developed, notably Cel could amplify copper death by scavenging GSH content. In addition, this self-amplified copper death further activates ICD, eliciting a powerful immune response. Although Cel has good anti-tumor activity, the Cel has poor water solubility and low bioavailability, has narrow treatment window and high overlapping degree of effective dose and toxic dose, and serious adverse reactions such as liver and kidney function injury and the like caused by specific distribution, so that the clinical transformation of Cel is severely restricted. Disclosure of Invention (One) solving the technical problems In view of the above, it is one of the main objectives of the present invention to provide a β -diketone iridium complex, and its preparation method and application. The beta-diketo iridium complex provided by the invention has high phototoxicity and low dark toxicity, can be used as an effective PS of PDT (PDT) to be applied to tumor cells, and is specifically delivered to the tumor cells by taking a traditional Chinese medicine monomer tripterine as a supplement and combining with a nano targeting delivery technology, so that the beta-diketo iridium complex is used for photodynamic/immune cooperative treatment of hypoxic tumors. (II) technical scheme In order to achieve the above object, the present invention provides a β -diketopyrrolopyrrole complex (Ir-O) having a structure represented by formula (I); Formula (I). In one embodiment, the β -diketiminate iridium complex further includes pharmaceutically acceptable salts, esters, hydrates, solvates, metabolites, prodrugs, stereoisomers, tautomers, polymorphs, and/or isotopic derivatives thereof. The invention also provides a preparation method of the beta-diketone iridium complex, which comprises the following steps: s1, reacting 3-ethoxy-4-h