New anthra[2,3-b]furancarboxamides: A role of positioning of the carboxamide moiety in antitumor properties

Radiation therapy with heavy particles including neutrons, an otherwise therapeutically perspective because of its high tissue penetration and efficient tumor damage, is currently limited by the lack of adequate equipment. An NG-24 generator (140 kg, 42 110 cm, ~1011 particles/s, 14 MeV) has been designed and engineered to replace the huge and environmentally harmful neutron reactors, cyclotrons, and accelerators with a compact, portable, safe, and potent source of high-energy neutrons. We demonstrate that the neutron beam produced by NG-24 causes a significant antiproliferative effect on human tumor cell lines regardless of the status of the anti-apoptotic p53 protein. Phosphorylation of histone 2A and increased amounts of p21, cyclin D, and phospho-p53 were detectable in HCT116 colon carcinoma cells (wild-type p53) irradiated with 4 Gy several days post-treatment, accompanied by G2/M phase arrest. These treatments dramatically reduced the ability of single cells to form colonies. In the HCT116p53KO subline (p53 -/-), the G2/M arrest was independent of the aforementioned mechanisms. Hence, the NG-24 generator is a source of a powerful, therapeutically relevant neutron flux that triggers a p53-independent antiproliferative response in tumor cells.

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“…The antibodies were purchased from Cell Signaling (USA). The protocols have been published in our earlier papers [10-12].…”

Section: Methodsmentioning

confidence: 99%

A Unique Prototypic Device for Radiation Therapy: The p53-Independent Antiproliferative Effect of Neutron Radiation

Yurkov

Syromukov

Tatarskiy³

et al. 2019

Acta Naturae

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“…Changing the acridine core to anthracene‐9, 10‐dione gives an additional class of G4 stabilizers. The size of the backbone and the number of side arms on the backbone structure also affect the binding efficiency and selectivity of the G4 stabilizers to telomeric DNA . Different structures of anthrone derivatives ( 61 ) are shown in Figure .…”

Section: G‐quadruplex Stabilizermentioning

confidence: 99%

Therapeutic strategies for targeting telomerase in cancer

Chen

Tang

Shi

et al. 2019

Medicinal Research Reviews

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Telomere and telomerase play important roles in abnormal cell proliferation, metastasis, stem cell maintenance, and immortalization in various cancers. Therefore, designing of drugs targeting telomerase and telomere is of great significance. Over the past two decades, considerable knowledge regarding telomere and telomerase has been accumulated, which provides theoretical support for the design of therapeutic strategies such as telomere elongation. Therefore, the development of telomere‐based therapies such as nucleoside analogs, non‐nucleoside small molecules, antisense technology, ribozymes, and dominant negative human telomerase reverse transcriptase are being prioritized for eradicating a majority of tumors. While the benefits of telomere‐based therapies are obvious, there is a need to address the limitations of various therapeutic strategies to improve the possibility of clinical applications. In this study, current knowledge of telomere and telomerase is discussed, and therapeutic strategies based on recent research are reviewed.

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“…Heteroarenanthracenediones containing cyclic diamines in the side chain are known to have high antiproliferative activity [ 1 , 2 , 3 , 4 , 5 ]. Previously described multi-targeting ( S )-3-[(3-amino-1-pyrrolidinyl)carbonyl]-4,11-dihydroxy-2-methylantra[2,3- b ]furan-5,10-dione (hereinafter anthrafuran) is capable of simultaneously inhibiting topoisomerase 1 and 2, as well as protein kinases, and induces the death of tumor cells of various histogenesis [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Subchronic Toxicity Study of Oral Anthrafuran on Rabbits

et al. 2021

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A new antitumor multi-target drug anthrafuran, with cellular targets such as topoisomerase I/II and some protein kinases, was obtained in Gause Institute of New Antibiotics and was demonstrated to have a reliable specific effect on different murine and human tumor models by oral administration. In this study, we focused on the evaluation of subchronic toxicity of oral anthrafuran drug formulation (AF) on Chinchilla rabbits. The absence of any changes in the condition or behavior of animals was shown for oral anthrafuran. Changes with reversible and dose-dependent hepato- and nephrotoxicity at low doses, as well as hemato- and gastrointestinal toxicity at high doses, were confirmed pathomorphologically. The identified toxic properties are extremely valuable, since oral anthrafuran does not have the limiting cardio- and myelotoxicity. Anthrafuran with 2 mg/kg/day or 6 mg/kg/day doses was administrated orally over 15 days. Investigations include assessment of the body weight, hematological and serum biochemical parameters and urinalysis, electrocardiography and pathomorphological evaluation of the internal organs. Quantitative data were processed statistically with Student’s t-Test, p < 0.05. Revealed during the subchronic study were the favorable toxicological properties of oral anthrafuran as opposed to clinical anthracyclines, oral idarubicin, or parenteral doxorubicin, which allows it to be considered promising for further research.

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New anthra[2,3-b]furancarboxamides: A role of positioning of the carboxamide moiety in antitumor properties

Cited by 29 publications

References 52 publications

A Unique Prototypic Device for Radiation Therapy: The p53-Independent Antiproliferative Effect of Neutron Radiation

A Unique Prototypic Device for Radiation Therapy: The p53-Independent Antiproliferative Effect of Neutron Radiation

Therapeutic strategies for targeting telomerase in cancer

Subchronic Toxicity Study of Oral Anthrafuran on Rabbits

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