New antitumor anthra[2,3-b]furan-3-carboxamides: Synthesis and structure-activity relationship

Тихомиров, А. С.; Lin, Chia-Yang; Volodina, Yulia L.; Dezhenkova, Lyubov G.; Tatarskiy, Victor V.; Schols, Dominique; Shtil, Alexander А.; Kaur, Punit; Chueh, Pin Ju; Shchekotikhin, Andrey E.

doi:10.1016/j.ejmech.2018.02.027

Cited by 29 publications

(21 citation statements)

References 34 publications

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“…First-line HCC treatment compounds such as doxorubicin are associated with systemic toxicity, inefficacy, and chemoresistance (10, 11). Recently, new anti-cancer compounds with high antiproliferative activity against chemoresistant cells have been developed (241, 242). The human tNOX gene encodes for a protein that is expressed in multiple solid malignancies where it is crucial for cellular migration and proliferation.…”

Section: Implications Of Sirt1 In the Treatment And Chemoresistance Omentioning

confidence: 99%

SIRT1 in the Development and Treatment of Hepatocellular Carcinoma

et al. 2019

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Current treatment options for inoperable HCCs have decreased therapeutic efficacy and are associated with systemic toxicity and chemoresistance. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide–dependent enzyme that is frequently overexpressed in HCC, where it promotes tumorigenicity, metastasis, and chemoresistance. SIRT1 also maintains the tumorigenic and self-renewal proprieties of liver cancer stem cells. Multiple tumor-suppressive microRNAs (miRNAs) are downregulated in HCC and, as a consequence, permit SIRT1-induced tumorigenicity. However, either directly targeting SIRT1, combining conventional chemotherapy with SIRT1 inhibitors, or upregulating tumor-suppressive miRNAs may improve therapeutic efficacy and patient outcomes. Here, we present the interaction between SIRT1, miRNAs, and liver cancer stem cells and discuss the consequences of their interplay for the development and treatment of HCC.

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Section: Implications Of Sirt1 In the Treatment And Chemoresistance Omentioning

confidence: 99%

SIRT1 in the Development and Treatment of Hepatocellular Carcinoma

et al. 2019

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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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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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“…These compounds interact with several intracellular targets involved in cancer progression including topoisomerases, telomerase, protein kinases, and G-quadruplex structures of nucleic acids [12]. Among the newly synthesized derivatives we identified (S)-3-(3-aminopyrrolidine-1-carbonyl)-4,11-dihydroxy-2-methylanthra [2,3-b]furan-5,10dione (anthrafuran, Figure 1) as the hit compound with submicromolar potency for several tumor cell lines [13,14]. Importantly, anthrafuran is also efficient against tumor cells with the molecular determinants of altered drug response such as the multidrug resistance (MDR) transporter P-glycoprotein (Pgp) or inactivation of p53.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, anthrafuran is also efficient against tumor cells with the molecular determinants of altered drug response such as the multidrug resistance (MDR) transporter P-glycoprotein (Pgp) or inactivation of p53. Anthrafuran induced apoptosis via inhibition of topoisomerases I/II, Aurora B protein kinase, and generation of oxidative stress [13,14]. The anticancer potency of 1 administrated intraperitoneally (i.p.)…”

Section: Introductionmentioning

confidence: 99%

Experimental Evaluation of Anticancer Efficiency and Acute Toxicity of Anthrafuran for Oral Administration

et al. 2020

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The new antitumor agent anthrafuran has demonstrated a consistent effect in murine tumor models when administered parenterally due to the simultaneous inhibition of multiple cellular targets such as topoisomerases I/II and protein kinases. In this study, we assessed the anticancer efficiency and acute toxicity of anthrafuran administered orally. The action of anthrafuran was studied on transplanted tumor models which included P388 leukemia, Ca755 mammary adenocarcinoma, LLC lung carcinoma, and T47D human breast cancer xenografts on Balb/c nude mice. A significant antitumor efficacy of oral anthrafuran was revealed for all tested tumor models as follows: T/Cmax = 219% for P388, TGImax = 91% for Ca755, TGImax = 84% with CRmax = 54% for LLC, and T/C = 38% for T47D. The optimal treatment schedule of orally administered anthrafuran was 70–100 mg/kg given daily for five days. The LD50 value of orally administered anthrafuran (306.7 mg/kg) in mice was six times higher than that for i.p. administration (52.5 mg/kg). The rates of antitumor efficacy and acute toxicity indicate the high potential for further research on anthrafuran as a new original oral anticancer multitarget agent with an expected satisfactory tolerability and bioavailability.

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New antitumor anthra[2,3-b]furan-3-carboxamides: Synthesis and structure-activity relationship

Cited by 29 publications

References 34 publications

SIRT1 in the Development and Treatment of Hepatocellular Carcinoma

SIRT1 in the Development and Treatment of Hepatocellular Carcinoma

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

Experimental Evaluation of Anticancer Efficiency and Acute Toxicity of Anthrafuran for Oral Administration

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