Other Anticancer Drugs Targeting DNA and DNA-Associated Enzymes

Avendaño, Carmen; Menéndez, J. Carlos

doi:10.1016/b978-0-444-62649-3.00007-7

Cited by 3 publications

(3 citation statements)

References 196 publications

(111 reference statements)

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“…Many studies have proven that olivacine, ellipticine, and their derivatives can interact with DNA and those interactions are omni-directional [49,50]. They interact with DNA by various mechanisms, the main ones being intercalation with DNA and inhibition of topoisomerase II activity [4][5][6].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Tylińska

Dobosz

Spychała

et al. 2021

IJMS

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Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Tylińska

Dobosz

Spychała

et al. 2021

IJMS

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“…The yield at that step increased to 85%. Our tosylation procedure gave an almost quantitative yield (8). At the final cyclization stage to 9-bromoellipticine (1), we used dioxane in the presence of HCl, which allowed us to avoid the chromatographic purification and to increase the cyclization yield significantly, up to 76%.…”

Section: Preparation Of 9-bromo-511-dimethyl-6h-pyrido[43-b]carbazole (1)mentioning

confidence: 99%

“…Thus, ellipticine exhibits a multimodal cytotoxic activity, which is not clearly specified. A biooxidation pathway was originally proposed [8], suggesting that ellipticine could serve as a substrate for peroxidases in vivo. Stiborová's group demonstrated that ellipticine covalently binds to DNA after being enzymatically activated with cytochromes P450 or peroxidases [9].…”

Section: Introductionmentioning

confidence: 99%

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

et al. 2020

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Cancer still remains a major public health concern around the world and the search for new potential antitumor molecules is essential for fighting the disease. This study evaluated the anticancer and immunomodulatory potential of the newly synthetized ellipticine derivate: sodium bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate (Br-Ell-SO3Na). It was prepared by the chlorosulfonation of 9-bromoellipticine. The ellipticine-7-sulfonic acid itself is not soluble, but its saponification with sodium hydroxide afforded a water-soluble sodium salt. The cytotoxicity of Br-Ell-SO3Na was tested against cancerous (K562 cell line) and non-cancerous cells (Vero cell line and human peripheral blood mononuclear cells (PBMC)) using a Methylthiazoletetrazolium (MTT) assay. Cell cycle arrest was assessed by flow cytometry and the immunomodulatory activity was analyzed through an enzyme-linked immunosorbent assay (ELISA). The results showed that the Br-Ell-SO3Na molecule has specific anticancer activity (IC50 = 35 µM) against the K562 cell line, once no cytotoxicity effect was verified against non-cancerous cells. Cell cycle analysis demonstrated that K562 cells treated with Br-Ell-SO3Na were arrested in the phase S. Moreover, the production of IL-6 increased and the expression of IL-8 was inhibited in the human PBMC treated with Br-Ell-SO3Na. The results demonstrated that Br-Ell-SO3Na is a promising anticancer molecule attested by its noteworthy activity against the K562 tumor cell line and immunomodulatory activity in human PBMC cells.

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Ellipticine, its Derivatives: Re-evaluation of Clinical Suitability with the Aid of Drug Delivery Systems

Dan

Varghese

Viswanathan

et al. 2020

CCDT

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Targeted drug delivery systems gave newer dimensions for safer and more effective use of therapeutic drugs, thus helping in circumventing the issues of toxicity and unintended drug accumulation. These ongoing developments in delivery systems can, in turn, bring back drugs that suffered various limitations, Ellipticine (EPT) being a candidate. EPT derivatives witnessed entry into clinical settings but failed to survive in clinics citing various toxic side effects. A large body of preclinical data deliberates the potency of drug delivery systems in increasing the efficiency of EPT/derivatives while decreasing their toxic side effects. Recent developments in drug delivery systems provide a platform to explore EPT and its derivatives as good clinical candidates in treating tumors. The present review deals with delivery mechanisms of EPT/EPT derivatives as antitumor drugs, in vitro and in vivo, and evaluates the suitability of EPT-carriers in clinical settings.

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Other Anticancer Drugs Targeting DNA and DNA-Associated Enzymes

Cited by 3 publications

References 196 publications

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

Ellipticine, its Derivatives: Re-evaluation of Clinical Suitability with the Aid of Drug Delivery Systems

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