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New Indazole Derivatives as Potential Scaffolds for the Development of Anticancer, Antiviral, and Anti-tuberculosis Chemotherapeutic Compounds Научная публикация

Журнал Current Medicinal Chemistry
ISSN: 0929-8673
Вых. Данные Год: 2026, Том: 33, Номер: 5, Страницы: 1021 - 1034 Страниц : 14 DOI: 10.2174/0109298673389070250822065247
Авторы Khandazhinskaya Anastasia 1 , Kondrashova Evgenya 1 , Sokhraneva Vera 1 , Novikova Olga 2 , Velikorodnaya Yulia 2 , Gorshenin Andrey 2 , Andreevskaya Sofia 3 , Smirnova Tatyana 3 , Moroz Maxim 4 , Kirillov Ilya 5 , Fedyakina Irina 5 , Chizhov Alexandr 6 , Kochetkov Sergey 1 , Matyugina Elena 1
Организации
1 Laboratory of Molecular Basis of Action of physiologically active compounds, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia
2 Laboratory of Immunology, Research Institute of Hygiene, Toxicology and Occupational Pathology, Federal Medical and Biological Agency, 400048, Volgograd, Russia
3 Microbiology Department, Central Tuberculosis Research Institute, 107564, Moscow, Russia
4 Medical school, Peoples’ Friendship University of Russia Named after Patrice Lumumba, 117198, Moscow, Russia
5 Laboratory of virus ecology, Gamaleya National Research Center for Epidemiology and Microbiology, Russian Ministry of Health, 123098, Moscow, Russia
6 Laboratory of mass spectrometry, Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Moscow, Russia

Информация о финансировании (1)

1

Реферат: 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.
Библиографическая ссылка: Khandazhinskaya A. , Kondrashova E. , Sokhraneva V. , Novikova O. , Velikorodnaya Y. , Gorshenin A. , Andreevskaya S. , Smirnova T. , Moroz M. , Kirillov I. , Fedyakina I. , Chizhov A. , Kochetkov S. , Matyugina E.
New Indazole Derivatives as Potential Scaffolds for the Development of Anticancer, Antiviral, and Anti-tuberculosis Chemotherapeutic Compounds
Current Medicinal Chemistry. 2026. V.33. N5. P.1021 - 1034. DOI: 10.2174/0109298673389070250822065247 WOS OpenAlex
Идентификаторы БД:
Web of science: WOS:001599399100001
OpenAlex: W4414072538
Цитирование в БД: Пока нет цитирований
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