Siddaram Nadigar,Rohith Gattu,Sanjay Ramesh,Rekha N Dharmappa,Vijendra Kumar Nanjundaswamy,Suhas Ramesh
{"title":"一类新型强效抗血管生成和抗氧化吡唑:合成、生物活性、对接和 ADMET 研究。","authors":"Siddaram Nadigar,Rohith Gattu,Sanjay Ramesh,Rekha N Dharmappa,Vijendra Kumar Nanjundaswamy,Suhas Ramesh","doi":"10.1080/17568919.2024.2394020","DOIUrl":null,"url":null,"abstract":"Aim: Angiogenesis is the hallmark of cancer progression driven by VEGF/VEGFR-2 signalling pathway, inhibition of which could be a solution to tackle the progression of tumour cells and thus arresting their growth.Materials & methods: A novel class of pyrazoles was synthesized using arginine and dibromo ketones. Antiangiogenic activity was performed by in vivo yolk sac method. Antioxidant activity was evaluated by hydroxyl and superoxide radical scavenging assays. Docking studies were performed to determine the pyrazoles' binding potential with VEGFR-2 receptor and VEGF tyrosine kinase. ADMET properties were calculated using SwissADME and admetSAR for drug-likeness.Results: Compounds 5a-e showed significant antiangiogenic effects. Compound 5f exhibited effective hydroxyl and superoxide radical scavenging activities. Docking results confirmed the potential binding efficiency with VEGFR-2 receptor over VEGF tyrosine kinase, thus, functioning as competitive-inhibitors. ADMET studies revealed that the compounds possess favourable drug-like qualities.Conclusion: This study presents a novel class of pyrazoles as promising antioxidant and antiangiogenic agents with favourable drug-likeness properties.","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":"88 1","pages":"1-16"},"PeriodicalIF":3.2000,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A novel class of potent antiangiogenic and antioxidant pyrazoles: synthesis, bioactivity, docking and ADMET studies.\",\"authors\":\"Siddaram Nadigar,Rohith Gattu,Sanjay Ramesh,Rekha N Dharmappa,Vijendra Kumar Nanjundaswamy,Suhas Ramesh\",\"doi\":\"10.1080/17568919.2024.2394020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Aim: Angiogenesis is the hallmark of cancer progression driven by VEGF/VEGFR-2 signalling pathway, inhibition of which could be a solution to tackle the progression of tumour cells and thus arresting their growth.Materials & methods: A novel class of pyrazoles was synthesized using arginine and dibromo ketones. Antiangiogenic activity was performed by in vivo yolk sac method. Antioxidant activity was evaluated by hydroxyl and superoxide radical scavenging assays. Docking studies were performed to determine the pyrazoles' binding potential with VEGFR-2 receptor and VEGF tyrosine kinase. ADMET properties were calculated using SwissADME and admetSAR for drug-likeness.Results: Compounds 5a-e showed significant antiangiogenic effects. Compound 5f exhibited effective hydroxyl and superoxide radical scavenging activities. Docking results confirmed the potential binding efficiency with VEGFR-2 receptor over VEGF tyrosine kinase, thus, functioning as competitive-inhibitors. ADMET studies revealed that the compounds possess favourable drug-like qualities.Conclusion: This study presents a novel class of pyrazoles as promising antioxidant and antiangiogenic agents with favourable drug-likeness properties.\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":\"88 1\",\"pages\":\"1-16\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Future medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17568919.2024.2394020\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17568919.2024.2394020","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
A novel class of potent antiangiogenic and antioxidant pyrazoles: synthesis, bioactivity, docking and ADMET studies.
Aim: Angiogenesis is the hallmark of cancer progression driven by VEGF/VEGFR-2 signalling pathway, inhibition of which could be a solution to tackle the progression of tumour cells and thus arresting their growth.Materials & methods: A novel class of pyrazoles was synthesized using arginine and dibromo ketones. Antiangiogenic activity was performed by in vivo yolk sac method. Antioxidant activity was evaluated by hydroxyl and superoxide radical scavenging assays. Docking studies were performed to determine the pyrazoles' binding potential with VEGFR-2 receptor and VEGF tyrosine kinase. ADMET properties were calculated using SwissADME and admetSAR for drug-likeness.Results: Compounds 5a-e showed significant antiangiogenic effects. Compound 5f exhibited effective hydroxyl and superoxide radical scavenging activities. Docking results confirmed the potential binding efficiency with VEGFR-2 receptor over VEGF tyrosine kinase, thus, functioning as competitive-inhibitors. ADMET studies revealed that the compounds possess favourable drug-like qualities.Conclusion: This study presents a novel class of pyrazoles as promising antioxidant and antiangiogenic agents with favourable drug-likeness properties.
期刊介绍:
Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.