Synthesis of 8-hydroxyquinoline glycoconjugates and preliminary assay of their β1,4-GalT inhibitory and anti-cancer properties

Krawczyk, M; Pastuch-Gawołek, Gabriela; Mrozek-Wilczkiewicz, Anna; Kuczak, Michał; Skonieczna, Magdalena; Musioł, Robert

doi:10.1016/j.bioorg.2018.11.047

Cited by 39 publications

(39 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have recently shown that the 1,2,3-triazole ring is an important element for glycoconjugate activity [54] (Figure 1). Except for the role of a connection between two active groups, it also has other interesting properties.…”

Section: Introductionmentioning

confidence: 99%

“…The general structure of the planned glycoconjugates is shown in Figure 2. It was decided to reverse the direction of linking reactive moieties compared to the previously reported glycoconjugates [54], consisting of sugar azides and propargyl derivatives of 8-HQ (Figure 1) and see how this will affect the activity of glycoconjugates. In addition, it was decided to check how the structure modification of the linker of the quinoline glycoconjugates affects their biological properties.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds

et al. 2019

Self Cite

View full text Add to dashboard Cite

Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of β-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…A new series of glycoconjugates composed of various sugar units ( 40 , 41 ) ( d -glucose or d -galactose) and 8-hydroxyquinolines ( 42 , 43 ) was prepared in an effective and simple method [ 29 ]. The connection between these units was accomplished by O -glycosidic bond or via O -methylene 1,2,3-triazole linker, as shown in Scheme 11 .…”

Section: Anticancer Activitymentioning

confidence: 99%

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines

2020

View full text Add to dashboard Cite

Compounds containing the 8-hydroxyquinoline (8-HQ) 1 nucleus exhibit a wide range of biological activities, including antimicrobial, anticancer, and antifungal effects. The chemistry and biology of this group have attracted the attention of chemists, medicinal chemists, and professionals in health sciences. A number of prescribed drugs incorporate this group, and numerous 8-HQ- based molecules can be used to develop potent lead compounds with good efficacy and low toxicity. This review focusses on the recent advances in the synthesis of 8-HQ derivatives with different pharmacological properties, including anticancer, antiviral, and antibacterial activities. For this purpose, recent relevant references were searched in different known databases and search engines, such as MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, Scientific Information Database (SID), SciFinder, and Institute for Scientific Information (ISI) Web of Knowledge. This review article provides a literature overview of the various synthetic strategies and biological activities of 8-HQ derivatives and covers the recent related literature. Taken together, compounds containing the 8-HQ moiety have huge therapeutic value and can act as potential building blocks for various pharmacologically active scaffolds. In addition, several described compounds in this review could act leads for the development of drugs against numerous diseases including cancer.

show abstract

“…Qiu et al proved that NF-κB inhibitor BAY11-7082 blocks NF-κB transcription, and ER-mediated induction of cell proliferation upon its activity was reversed [21]. These data are useful in the development of therapy strategies for IBC, with ER-positive breast tumors usually resistant to endocrine therapy [24,25,26]. In the line with this evidence, the search for new potential inhibitors of NF-κB is necessary.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative Aspect of Benzimidazole Derivatives’ Activity and Their Impact on NF-κB Expression

Błaszczak-Świątkiewicz

2019

Molecules

View full text Add to dashboard Cite

Benzimidazoles belong to a new class of bioreductive agents with cytotoxic activity towards solid tumor cells, especially in their first stage of growth, which is characterized by low oxygen concentration. Bioreductive agents represent a class of prodrugs that target hypoxic tumor cells. Their bioactivity depends on the reactivity of their functional chemical groups. Their efficacy requires metabolic reduction and subsequent generation of toxic prodrugs. Chemoresistance of tumor cells is a major problem for successful antitumor therapy for many types of tumors, especially for breast cancer. The present study was performed to assess the effect of the antiproliferation activity of the tested benzimidazoles by way of NF-κB expression inhibition. The activity of the tested compounds on T47D and MCF7 cells was examined by WST, western blot, NF-κB transactivation assay, and apoptotic cell population analysis. Compound 3 was highly cytotoxically active against T47D cells, especially in hypoxic conditions. Its IC50 of 0.31 ± 0.06 nM, although weaker than tirapazamine, was significantly higher than the other tested compounds (2.4–3.0 fold). The increased bax protein expression upon exposure to the tested compounds indicated intercellular apoptotic pathway activity, with tumor cell death by way of apoptosis. Increased bax protein synthesis and apoptotic cell dominance upon treatment, especially with N-oxide derivatives (92% apoptotic cells among T47D cell populations during treatment with compound 3), were correlated with each other. Additionally, both increased bax protein and decreased NF-κB protein expression supported antiproliferative activity via NF-κB–DNA binding inhibition associated with the tested compounds. Compound 3 appeared to be the strongest inhibitor of NF-κB expression in hypoxic conditions (the potency against NF-κB expression was about 75% of that of tirapazamine). The present studies involving this class of heterocyclic small molecules proved their potential usefulness in anticancer therapy as compounds be able to limit tumor cell proliferation and reverse drug resistance by NF-κB repression.

show abstract

Synthesis of 8-hydroxyquinoline glycoconjugates and preliminary assay of their β1,4-GalT inhibitory and anti-cancer properties

Cited by 39 publications

References 81 publications

8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds

8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds

Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines

Antiproliferative Aspect of Benzimidazole Derivatives’ Activity and Their Impact on NF-κB Expression

Contact Info

Product

Resources

About