2-Amino-Pyrrole-Carboxylate Attenuates Homology-Mediated DNA Repair and Sensitizes Cancer Cells to Doxorubicin

Boichuk, Sergei; Bikinieva, Firuza; Мустафин, И Г; Зыкова, С. С.; Ryzkin, Sergei; Galembikova, Aigul

doi:10.1134/s0006297922050017

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Additionally, 2-Amino-Pyrrole-Carboxylate (2-APC) amplifies doxorubicin (DOX) cytotoxicity by inhibiting DNA damage repair via Rad51 recombinase reduction. These intricate combinatorial strategies showcase the evolving landscape of anticancer research, emphasizing the interconnected roles of DNA repair proteins and topo-active drugs [185,186].…”

Section: Dna Damage Response Pathways and Topo-active Drug Resistancementioning

confidence: 99%

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Sharma,

Bahot,

Sekar

et al. 2024

Cancers

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In recent years, the emergence of cancer drug resistance has been one of the crucial tumor hallmarks that are supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters, and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often result in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores the use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

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Section: Dna Damage Response Pathways and Topo-active Drug Resistancementioning

confidence: 99%

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Sharma,

Bahot,

Sekar

et al. 2024

Cancers

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“…2-Amino-Pyrrole-Carboxylate (2-APC) dramatically increases doxorubicin cytotoxicity and promotes apoptosis in cancer cells at non-toxic concentrations. This was due to 2-APC's ability to inhibit DNA damage repair by reducing the amount of Rad51 recombinase via proteasomal degradation [185,186].…”

Section: Dna Damage Response Pathways and Topo-active Drug Resistancementioning

confidence: 99%

Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Sinha

2023

Preprint

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In recent years, the emergence of cancer drug resistance is one of the crucial tumor hallmarks which is supported by the level of genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression of ABC transporters and stemness are among the several key contributing molecular and cellular response mechanisms. Topo-active drugs, e.g., doxorubicin and topotecan, are clinically active and are utilized extensively against a wide variety of human tumors and often results in the development of resistance and failure to therapy. Thus, there is an urgent need for an incremental and comprehensive understanding of mechanisms of cancer drug resistance specifically in the context of topo-active drugs. This review delves into the intricate mechanistic aspects of these intracellular and extracellular topo-active drug resistance mechanisms and explores use of potential combinatorial approaches by utilizing various topo-active drugs and inhibitors of pathways involved in drug resistance. We believe that this review will help guide basic scientists, pre-clinicians, clinicians, and policymakers toward holistic and interdisciplinary strategies that transcend resistance, renewing optimism in the ongoing battle against cancer.

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“…При разработке нового метода определения антиоксидантной активности in vitro использовались результаты ДФПГ-теста антирадикальной активности для определения сходимости с результатами классических in vitro тестов антиоксидантной активности, а также квантово-химические расчеты, позволяющие оценить реакционную способность соединений в биологических системах за счет определения физико-химических параметров мо-лекулы. Исследование антиоксидантной и антирадикальной активности 2-аминопирролов дополняет актуальность исследования, поскольку позволяет раскрыть возможности перспективной группы веществ-цитостатиков, действие которых на опухолевую ткань может быть дополнено нарушением патологического баланса свободных форм кислорода [7][8][9][10].…”

Section: Introductionunclassified

Study of Antioxidant Activity and Quantum-chemical Calculations of 2-aminopyrroles

Зыкова

Gankova

Shustov

et al. 2022

Razrabotka i registraciâ lekarstvennyh sredstv

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Introduction. Modern therapy defines oxidative stress as one of the key links in the pathogenesis of different diseases, which makes the search for new low molecular weight antioxidants actual [1]. The widely used methods are imperfect, since they reflects reactivity of the sample under artificial conditions [2–4]. The proposed technique of using the "Ecolum" biosensor makes it possible to preserve the advantages of in vitro methods and improve the accuracy of determination through the use of biological reactions of cells [5, 6].Aim. Studying of the antiradical and antioxidant activity of 2-aminopyrroles, using in vitro methods and quantum-chemical calculations. Materials and methods. Earlier, derivatives of 2-aminopyrroles were obtained. Antiradical activity of the compounds was studied using the DPPH test (2,2-diphenyl-1-picrylhydrazyl). Antioxidant activity was evaluated on the model of oxidative stress using the «Ecolum» biosensor. The calculation data of the indices of reactivity in the approximation of the gas phase were obtained using quantum-chemical methods.Results and discussion. The antioxidant activity test indicated a higher antioxidant potential of 2a, compared to 2b. Antiradical activity test revealed a greater antiradical potential of 2b. Quantum-chemical calculations showed that 2b is characterized by a higher ionization potential, which may indicate its greater resistance to oxidation compared to 2a.Conclusion. The study of the antiradical and antioxidant activity of 2-aminopyrroles showed the importance of developing a methodology for the search for new antioxidants, because of antiradical activity test deviations, compared to living cell reactions.

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2-Amino-Pyrrole-Carboxylate Attenuates Homology-Mediated DNA Repair and Sensitizes Cancer Cells to Doxorubicin

Cited by 4 publications

References 32 publications

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review

Study of Antioxidant Activity and Quantum-chemical Calculations of 2-aminopyrroles

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