{"title":"对合成和半合成黄嘌呤氧化酶抑制剂的全面回顾:根据硅内计算的 ADME 特征确定潜在线索。","authors":"Rupali Rana, Anchal Sharma, Nitish Kumar, Aanchal Khanna, Jyoti, Muskan Dhir, Harmandeep Kaur Gulati, Jatinder Vir Singh, Preet Mohinder Singh Bedi","doi":"10.1007/s11030-024-10962-1","DOIUrl":null,"url":null,"abstract":"<p><p>Xanthine oxidase (XO) inhibitors, both synthetic and semisynthetic, have been developed extensively over the past few decades. The increased level of XO is not only the major cause of gout but is also responsible for various conditions associated with hyperuricemia, such as cardiovascular disorders, chronic kidney disorders, diabetes, Alzheimer's disease and chronic wounds. Marketed available XO inhibitors (allopurinol, febuxostat, and topiroxostat) are used to treat hyperuricemia but they are associated with fatal side effects, which pose serious problems for the healthcare system, rising the need for new, more potent, safer compounds. This review summarizes recent findings on XO and describes their design, synthesis, biological significance in the development of anti-hyperuricemic drugs with ADME profile, structure activity relationship (SAR) and molecular docking studies. The results might help medicinal chemists to develop more efficacious XO inhibitors.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A comprehensive review of synthetic and semisynthetic xanthine oxidase inhibitors: identification of potential leads based on in-silico computed ADME characteristics.\",\"authors\":\"Rupali Rana, Anchal Sharma, Nitish Kumar, Aanchal Khanna, Jyoti, Muskan Dhir, Harmandeep Kaur Gulati, Jatinder Vir Singh, Preet Mohinder Singh Bedi\",\"doi\":\"10.1007/s11030-024-10962-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Xanthine oxidase (XO) inhibitors, both synthetic and semisynthetic, have been developed extensively over the past few decades. The increased level of XO is not only the major cause of gout but is also responsible for various conditions associated with hyperuricemia, such as cardiovascular disorders, chronic kidney disorders, diabetes, Alzheimer's disease and chronic wounds. Marketed available XO inhibitors (allopurinol, febuxostat, and topiroxostat) are used to treat hyperuricemia but they are associated with fatal side effects, which pose serious problems for the healthcare system, rising the need for new, more potent, safer compounds. This review summarizes recent findings on XO and describes their design, synthesis, biological significance in the development of anti-hyperuricemic drugs with ADME profile, structure activity relationship (SAR) and molecular docking studies. The results might help medicinal chemists to develop more efficacious XO inhibitors.</p>\",\"PeriodicalId\":708,\"journal\":{\"name\":\"Molecular Diversity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Diversity\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s11030-024-10962-1\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-10962-1","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
摘要
过去几十年来,合成和半合成的黄嘌呤氧化酶(XO)抑制剂得到了广泛开发。XO 水平升高不仅是痛风的主要原因,也是各种与高尿酸血症有关的疾病的罪魁祸首,如心血管疾病、慢性肾脏疾病、糖尿病、老年痴呆症和慢性伤口。市场上现有的 XO 抑制剂(别嘌醇、非布司他和托吡罗司他)可用于治疗高尿酸血症,但它们会产生致命的副作用,给医疗保健系统带来严重问题,因此需要更强效、更安全的新化合物。本综述总结了有关 XO 的最新研究成果,介绍了它们的设计、合成、在开发抗高尿酸血症药物中的生物学意义、ADME 特征、结构-活性关系(SAR)和分子对接研究。这些结果可能有助于药物化学家开发出更有效的 XO 抑制剂。
A comprehensive review of synthetic and semisynthetic xanthine oxidase inhibitors: identification of potential leads based on in-silico computed ADME characteristics.
Xanthine oxidase (XO) inhibitors, both synthetic and semisynthetic, have been developed extensively over the past few decades. The increased level of XO is not only the major cause of gout but is also responsible for various conditions associated with hyperuricemia, such as cardiovascular disorders, chronic kidney disorders, diabetes, Alzheimer's disease and chronic wounds. Marketed available XO inhibitors (allopurinol, febuxostat, and topiroxostat) are used to treat hyperuricemia but they are associated with fatal side effects, which pose serious problems for the healthcare system, rising the need for new, more potent, safer compounds. This review summarizes recent findings on XO and describes their design, synthesis, biological significance in the development of anti-hyperuricemic drugs with ADME profile, structure activity relationship (SAR) and molecular docking studies. The results might help medicinal chemists to develop more efficacious XO inhibitors.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;