Novel multi-targeting anthra[2,3-b]thiophene-5,10-diones with guanidine-containing side chains: Interaction with telomeric G-quadruplex, inhibition of telomerase and topoisomerase I and cytotoxic properties

Ilyinsky, Nikolay S.; Shchyolkina, Anna K.; Borisova, O. F.; Мамаева, О. К.; Zvereva, Maria I.; Azhibek, Dulat; Livshits, M. A.; Mitkevich, Vladimir A.; Balzarini, Jan; Sinkevich, Yuri B.; Luzikov, Yu. N.; Dezhenkova, Lyubov G.; Kolotova, Ekaterina S.; Shtil, Alexander A.; Shchekotikhin, Andrey E.; Kaluzhny, Dmitry N.

doi:10.1016/j.ejmech.2014.08.030

Cited by 26 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That suggests that the ability to form G4 structures is not important for RNA for interactions with telomerase and competition with DNA binding sites. It is well known that the stabilization of G4s in telomere DNA by small molecules results in telomerase inhibition (Neidle, ; Ilyinsky et al ., ). Such inhibition can occur because of the lack of telomerase binding to stabilized G4 structures or could be a result of direct binding to a telomerase reverse transcriptase subunit.…”

Section: Discussionmentioning

confidence: 97%

TERRA mimicking ssRNAs prevail over the DNA substrate for telomerase in vitro due to interactions with the alternative binding site

Azhibek

Skvortsov

Andreeva

et al. 2015

J of Molecular Recognition

View full text Add to dashboard Cite

Telomerase is a key component of the telomere length maintenance system in the majority of eukaryotes. Telomerase displays maximal activity in stem and cancer cells with high proliferative potential. In humans, telomerase activity is regulated by various mechanisms, including the interaction with telomere ssDNA overhangs that contain a repetitive G-rich sequence, and with noncoding RNA, Telomeric repeat-containing RNA (TERRA), that contains the same sequence. So these nucleic acids can compete for telomerase RNA templates in the cell. In this study, we have investigated the ability of different model substrates mimicking telomere DNA overhangs and TERRA RNA to compete for telomerase in vitro through a previously developed telomerase inhibitor assay. We have shown in this study that RNA oligonucleotides are better competitors for telomerase that DNA ones as RNA also use an alternative binding site on telomerase, and the presence of 2'-OH groups is significant in these interactions. In contrast to DNA, the possibility of forming intramolecular G-quadruplex structures has a minor effect for RNA binding to telomerase. Taking together our data, we propose that TERRA RNA binds better to telomerase compared with its native substrate - the 3'-end of telomere DNA overhang. As a result, some specific factor may exist that participates in switching telomerase from TERRA to the 3'-end of DNA for telomere elongation at the distinct period of a cell cycle in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

show abstract

Section: Discussionmentioning

confidence: 97%

TERRA mimicking ssRNAs prevail over the DNA substrate for telomerase in vitro due to interactions with the alternative binding site

Azhibek

Skvortsov

Andreeva

et al. 2015

J of Molecular Recognition

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Thus, both compounds previously synthesized (5)(6)(7)(8) as the novel compounds (9)(10)(11)(12)(13)(14) were assessed for their pharmacological potential.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities

Oliveira

Silva

Vendramini–Costa

et al. 2015

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Novel multi-targeting anthra[2,3-b]thiophene-5,10-diones with guanidine-containing side chains: Interaction with telomeric G-quadruplex, inhibition of telomerase and topoisomerase I and cytotoxic properties

Cited by 26 publications

References 28 publications

TERRA mimicking ssRNAs prevail over the DNA substrate for telomerase in vitro due to interactions with the alternative binding site

TERRA mimicking ssRNAs prevail over the DNA substrate for telomerase in vitro due to interactions with the alternative binding site

Therapeutic strategies for targeting telomerase in cancer

Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities

Contact Info

Product

Resources

About