{"title":"新的吲哚唑衍生物作为抗癌、抗病毒和抗结核化疗化合物开发的潜在支架。","authors":"Khandazhinskaya Anastasia, Kondrashova Evgenya, Sokhraneva Vera, Novikova Olga, Velikorodnaya Yulia, Gorshenin Andrey, Andreevskaya Sofia, Smirnova Tatyana, Moroz Maxim, Kirillov Ilya, Fedyakina Irina, Chizhov Alexandr, Kochetkov Sergey, Matyugina Elena","doi":"10.2174/0109298673389070250822065247","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy remains essential despite advances in immunotherapy, radiotherapy, and biological therapy. However, the wide range of chemical drugs is limited by a narrow therapeutic index, low selectivity, and the development of resistance. In this regard, new high-efficiency drugs are in extremely high demand. The indazole moiety, a scaffold found in many biologically active compounds, was selected for use in new drug design.</p><p><strong>Methods: </strong>Six new indazole derivatives were synthesized via Suzuki-Miyaura coupling starting from bromoindazole. Their antiviral (against influenza A and SARS-CoV-2), antibacterial (against M. tuberculosis), and antiproliferative activities (against neuroblastoma, glioma, leukemia cell lines) were evaluated in vitro. Acute toxicity was assessed in mice of both sexes via single intragastric administration, with toxicometric parameters and pathomorphological changes studied.</p><p><strong>Results: </strong>6-(1H-pyrazol-4-yl)-1H-indazole (8) suppressed the reproduction of the influenza virus at non-toxic doses to the MDCK cells and showed cytotoxicity against cancer cell lines, with an IC50 between 4 and 14 μM. However, it exhibited significant acute toxicity in mice (LD50 40 mg/kg), causing systemic organ damage.</p><p><strong>Discussion: </strong>Derivative 8 demonstrated promising antiviral and antiproliferative activities but exhibited considerable acute toxicity in vivo. The antiviral efficacy, although lower than oseltamivir, is meaningful and justifies further optimization and investigation. Its antibacterial activity against M. tuberculosis adds to its potential as a multifunctional agent.</p><p><strong>Conclusion: </strong>While derivative 8 has shown potential as an antiviral and anticancer agent, its high toxicity highlights the need for further studies to define a safe and effective therapeutic window. Overall, the indazole scaffold remains a valuable platform for the development of new therapeutic compounds.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New Indazole Derivatives as Potential Scaffolds for the Development of Anticancer, Antiviral, and Anti-tuberculosis Chemotherapeutic Compounds.\",\"authors\":\"Khandazhinskaya Anastasia, Kondrashova Evgenya, Sokhraneva Vera, Novikova Olga, Velikorodnaya Yulia, Gorshenin Andrey, Andreevskaya Sofia, Smirnova Tatyana, Moroz Maxim, Kirillov Ilya, Fedyakina Irina, Chizhov Alexandr, Kochetkov Sergey, Matyugina Elena\",\"doi\":\"10.2174/0109298673389070250822065247\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Chemotherapy remains essential despite advances in immunotherapy, radiotherapy, and biological therapy. However, the wide range of chemical drugs is limited by a narrow therapeutic index, low selectivity, and the development of resistance. In this regard, new high-efficiency drugs are in extremely high demand. The indazole moiety, a scaffold found in many biologically active compounds, was selected for use in new drug design.</p><p><strong>Methods: </strong>Six new indazole derivatives were synthesized via Suzuki-Miyaura coupling starting from bromoindazole. Their antiviral (against influenza A and SARS-CoV-2), antibacterial (against M. tuberculosis), and antiproliferative activities (against neuroblastoma, glioma, leukemia cell lines) were evaluated in vitro. Acute toxicity was assessed in mice of both sexes via single intragastric administration, with toxicometric parameters and pathomorphological changes studied.</p><p><strong>Results: </strong>6-(1H-pyrazol-4-yl)-1H-indazole (8) suppressed the reproduction of the influenza virus at non-toxic doses to the MDCK cells and showed cytotoxicity against cancer cell lines, with an IC50 between 4 and 14 μM. However, it exhibited significant acute toxicity in mice (LD50 40 mg/kg), causing systemic organ damage.</p><p><strong>Discussion: </strong>Derivative 8 demonstrated promising antiviral and antiproliferative activities but exhibited considerable acute toxicity in vivo. The antiviral efficacy, although lower than oseltamivir, is meaningful and justifies further optimization and investigation. Its antibacterial activity against M. tuberculosis adds to its potential as a multifunctional agent.</p><p><strong>Conclusion: </strong>While derivative 8 has shown potential as an antiviral and anticancer agent, its high toxicity highlights the need for further studies to define a safe and effective therapeutic window. Overall, the indazole scaffold remains a valuable platform for the development of new therapeutic compounds.</p>\",\"PeriodicalId\":10984,\"journal\":{\"name\":\"Current medicinal chemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0109298673389070250822065247\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0109298673389070250822065247","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
New Indazole Derivatives as Potential Scaffolds for the Development of Anticancer, Antiviral, and Anti-tuberculosis Chemotherapeutic Compounds.
Introduction: Chemotherapy remains essential despite advances in immunotherapy, radiotherapy, and biological therapy. However, the wide range of chemical drugs is limited by a narrow therapeutic index, low selectivity, and the development of resistance. In this regard, new high-efficiency drugs are in extremely high demand. The indazole moiety, a scaffold found in many biologically active compounds, was selected for use in new drug design.
Methods: Six new indazole derivatives were synthesized via Suzuki-Miyaura coupling starting from bromoindazole. Their antiviral (against influenza A and SARS-CoV-2), antibacterial (against M. tuberculosis), and antiproliferative activities (against neuroblastoma, glioma, leukemia cell lines) were evaluated in vitro. Acute toxicity was assessed in mice of both sexes via single intragastric administration, with toxicometric parameters and pathomorphological changes studied.
Results: 6-(1H-pyrazol-4-yl)-1H-indazole (8) suppressed the reproduction of the influenza virus at non-toxic doses to the MDCK cells and showed cytotoxicity against cancer cell lines, with an IC50 between 4 and 14 μM. However, it exhibited significant acute toxicity in mice (LD50 40 mg/kg), causing systemic organ damage.
Discussion: Derivative 8 demonstrated promising antiviral and antiproliferative activities but exhibited considerable acute toxicity in vivo. The antiviral efficacy, although lower than oseltamivir, is meaningful and justifies further optimization and investigation. Its antibacterial activity against M. tuberculosis adds to its potential as a multifunctional agent.
Conclusion: While derivative 8 has shown potential as an antiviral and anticancer agent, its high toxicity highlights the need for further studies to define a safe and effective therapeutic window. Overall, the indazole scaffold remains a valuable platform for the development of new therapeutic compounds.
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Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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