{"title":"ttfa -铂偶联物：通过评价稳定性-活性关系解读复方前药的治疗作用。","authors":"Megha Biswas, Kanishka Chaudhary, Swati Shree Padhi, Arka Banerjee, R Selvi Bharathavikru, Sateesh Bandaru, Subhra Jyoti Panda, Chandra Shekhar Purohit, Nihar Ranjan Das, Rakesh Kumar Pathak","doi":"10.1021/acs.jmedchem.4c01545","DOIUrl":null,"url":null,"abstract":"<p><p>This work introduces a novel Pt(II) based prodrug TTFA-Platin that integrates a β-diketonate ligand TTFA with a platinum scaffold to structurally resemble carboplatin and offers intermediate kinetic lability between cisplatin and carboplatin, striking a balance between therapeutic efficacy and safety. A comprehensive stability and speciation study was conducted in various biological media, mapping the therapeutic effects of TTFA-Platin. A control molecule, TMK-Platin, was synthesized to further validate the structural-stability relationship, which displayed poor activatable features in biological systems. <i>In vitro</i> studies against a panel of cancer cell lines revealed that TTFA-Platin exhibited significantly higher potency compared to TMK-Platin. <i>In vivo</i> studies revealed that TTFA-Platin exhibited significantly lower toxicity than the reference platinum compounds. Thus, leveraging ligands that fine-tune kinetic lability and offer therapeutic benefits can help develop more effective and safer cancer treatments, addressing the limitations of existing therapies.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":" ","pages":"20986-21008"},"PeriodicalIF":6.8000,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TTFA-Platin Conjugate: Deciphering the Therapeutic Roles of Combo-Prodrug through Evaluating Stability-Activity Relationship.\",\"authors\":\"Megha Biswas, Kanishka Chaudhary, Swati Shree Padhi, Arka Banerjee, R Selvi Bharathavikru, Sateesh Bandaru, Subhra Jyoti Panda, Chandra Shekhar Purohit, Nihar Ranjan Das, Rakesh Kumar Pathak\",\"doi\":\"10.1021/acs.jmedchem.4c01545\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This work introduces a novel Pt(II) based prodrug TTFA-Platin that integrates a β-diketonate ligand TTFA with a platinum scaffold to structurally resemble carboplatin and offers intermediate kinetic lability between cisplatin and carboplatin, striking a balance between therapeutic efficacy and safety. A comprehensive stability and speciation study was conducted in various biological media, mapping the therapeutic effects of TTFA-Platin. A control molecule, TMK-Platin, was synthesized to further validate the structural-stability relationship, which displayed poor activatable features in biological systems. <i>In vitro</i> studies against a panel of cancer cell lines revealed that TTFA-Platin exhibited significantly higher potency compared to TMK-Platin. <i>In vivo</i> studies revealed that TTFA-Platin exhibited significantly lower toxicity than the reference platinum compounds. Thus, leveraging ligands that fine-tune kinetic lability and offer therapeutic benefits can help develop more effective and safer cancer treatments, addressing the limitations of existing therapies.</p>\",\"PeriodicalId\":46,\"journal\":{\"name\":\"Journal of Medicinal Chemistry\",\"volume\":\" \",\"pages\":\"20986-21008\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-12-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jmedchem.4c01545\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c01545","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
TTFA-Platin Conjugate: Deciphering the Therapeutic Roles of Combo-Prodrug through Evaluating Stability-Activity Relationship.
This work introduces a novel Pt(II) based prodrug TTFA-Platin that integrates a β-diketonate ligand TTFA with a platinum scaffold to structurally resemble carboplatin and offers intermediate kinetic lability between cisplatin and carboplatin, striking a balance between therapeutic efficacy and safety. A comprehensive stability and speciation study was conducted in various biological media, mapping the therapeutic effects of TTFA-Platin. A control molecule, TMK-Platin, was synthesized to further validate the structural-stability relationship, which displayed poor activatable features in biological systems. In vitro studies against a panel of cancer cell lines revealed that TTFA-Platin exhibited significantly higher potency compared to TMK-Platin. In vivo studies revealed that TTFA-Platin exhibited significantly lower toxicity than the reference platinum compounds. Thus, leveraging ligands that fine-tune kinetic lability and offer therapeutic benefits can help develop more effective and safer cancer treatments, addressing the limitations of existing therapies.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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