Neelaveni Thangavel, Mohammed Al Bratty, Sadique Akhtar Javed, Waquar Ahsan, Hassan A Alhazmi
{"title":"利用噻唑烷二酮靶向过氧化物酶体增殖物激活受体:新型降糖药的设计策略。","authors":"Neelaveni Thangavel, Mohammed Al Bratty, Sadique Akhtar Javed, Waquar Ahsan, Hassan A Alhazmi","doi":"10.1155/2017/1069718","DOIUrl":null,"url":null,"abstract":"<p><p>Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPAR<i>γ</i>, one of the subtypes of PPARs. Certain compounds under development have dual PPAR<i>α</i>/<i>γ</i> agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPAR<i>γ</i> agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPAR<i>γ</i> agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.</p>","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"1069718"},"PeriodicalIF":0.0000,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/1069718","citationCount":"58","resultStr":"{\"title\":\"Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs.\",\"authors\":\"Neelaveni Thangavel, Mohammed Al Bratty, Sadique Akhtar Javed, Waquar Ahsan, Hassan A Alhazmi\",\"doi\":\"10.1155/2017/1069718\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPAR<i>γ</i>, one of the subtypes of PPARs. Certain compounds under development have dual PPAR<i>α</i>/<i>γ</i> agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPAR<i>γ</i> agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPAR<i>γ</i> agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.</p>\",\"PeriodicalId\":14082,\"journal\":{\"name\":\"International Journal of Medicinal Chemistry\",\"volume\":\"2017 \",\"pages\":\"1069718\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1155/2017/1069718\",\"citationCount\":\"58\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/2017/1069718\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/6/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Medicinal Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2017/1069718","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/6/5 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs.
Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.
期刊介绍:
International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis. International Journal of Medicinal Chemistry is a peer-reviewed, Open Access journal that publishes original research articles as well as review articles in all areas of chemistry associated with drug discovery, design, and synthesis.