Synthesis and Cytotoxicity of 2,3-Enopyranosyl C-Linked Conjugates of Genistein

Szeja, W.; Grynkiewicz, Grzegorz; Bieg, Tadeusz; Świerk, Piotr; Byczek, Anna; Papaj, Katarzyna; Kitel, Radosław; Rusin, Aleksandra

doi:10.3390/molecules19067072

Cited by 13 publications

(8 citation statements)

References 43 publications

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“…Other authors (Szeja et al, 2014 [ 16 ]) reported that genistein-2,3-Enopyranosyl conjugate D was active against human cell lines HCT-116 and DU-145 with IC 50 values of 2.25 and 4.64 µM, respectively [ 16 ]. In addition, in a different investigation, it was reported that conjugate E showed high activity over three ER-positive breast cancer cell lines, MCF-7, 21PT and T47D, with IC 50 values of 0.8, 0.9 and 0.9 μM respectively.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

et al. 2022

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A series of 5-FU-Genistein hybrids were synthesized and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated in human colon adenocarcinoma cells (SW480 and SW620) and non-malignant cell lines (HaCaT and CHO-K1). Hybrid 4a displayed cytotoxicity against SW480 and SW620 cells with IC50 values of 62.73 ± 7.26 µM and 50.58 ± 1.33 µM, respectively; compound 4g induced cytotoxicity in SW620 cells with an IC50 value of 36.84 ± 0.71 µM. These compounds were even more selective than genistein alone, the reference drug (5-FU) and the equimolar mixture of genistein plus 5-FU. In addition, hybrids 4a and 4g induced time- and concentration-dependent antiproliferative activity and cell cycle arrest at the S-phase and G2/M. It was also observed that hybrid 4a induced apoptosis in SW620 cells probably triggered by the extrinsic pathway in response to the activation of p53, as evidenced by the increase in the levels of caspases 3/8 and the tumor suppressor protein (Tp53). Molecular docking studies suggest that the most active compound 4a would bind efficiently to proapoptotic human caspases 3/8 and human Tp53, which in turn could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. On the other hand, molecular dynamics (MD) studies provided strong evidence of the conformational stability of the complex between caspase-3 and hybrid 4a obtained throughout 100 ns all-atom MD simulation. Molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analyses of the complex with caspase-3 showed that the interaction between the ligand and the target protein is stable. Altogether, the results suggest that the active hybrids, mainly compound 4a, might act by modulating caspase-3 activity in a colorectal cancer model, making it a privileged scaffold that could be used in future investigations.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

et al. 2022

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“…The fact that up to three of them have the α-configuration at the sugar unit anomeric carbon is worth emphasizing. However, the length of the linker between the sugar fragment and genistein appears to have an equally significant impact on the demonstrated cytotoxicity [ 167 ]. On the basis of the research results described so far using an in vitro cell model, it can be noted that genistein glycoconjugates containing the O -glycosidic or C -glycosidic linkage show in most cases significantly higher antiproliferative activity in comparison to the genistein parent compound.…”

Section: Glycoconjugatesmentioning

confidence: 99%

A Small Sugar Molecule with Huge Potential in Targeted Cancer Therapy

et al. 2023

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The number of cancer-related diseases is still growing. Despite the availability of a large number of anticancer drugs, the ideal drug is still being sought that would be effective, selective, and overcome the effect of multidrug resistance. Therefore, researchers are still looking for ways to improve the properties of already-used chemotherapeutics. One of the possibilities is the development of targeted therapies. The use of prodrugs that release the bioactive substance only under the influence of factors characteristic of the tumor microenvironment makes it possible to deliver the drug precisely to the cancer cells. Obtaining such compounds is possible by coupling a therapeutic agent with a ligand targeting receptors, to which the attached ligand shows affinity and is overexpressed in cancer cells. Another way is to encapsulate the drug in a carrier that is stable in physiological conditions and sensitive to conditions of the tumor microenvironment. Such a carrier can be directed by attaching to it a ligand recognized by receptors typical of tumor cells. Sugars seem to be ideal ligands for obtaining prodrugs targeted at receptors overexpressed in cancer cells. They can also be ligands modifying polymers’ drug carriers. Furthermore, polysaccharides can act as selective nanocarriers for numerous chemotherapeutics. The proof of this thesis is the huge number of papers devoted to their use for modification or targeted transport of anticancer compounds. In this work, selected examples of broad-defined sugars application for improving the properties of both already-used drugs and substances exhibiting anticancer activity are presented.

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“…Compound 32 exhibited IC 50 value 2.28 and 4.64 μM whereas 33 showed IC 50 value 4.69 and 4.90 μM against HCT 116 and DU 145 cell lines respectively. Paclitaxel was used as reference drug that inhibited the proliferation of cell at low nanomolar concentrations [146] …”

Section: Semi‐synthetic Modification Of Genistein During the Period 2...mentioning

confidence: 99%

Therapeutic Potential of Genistein and its Derivatives as a Target for Anticancer Agents

Gupta

Kumar³

et al. 2023

ChemistrySelect

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Genistein is a natural isoflavone and a phytoestrogen known to possess broad range of pharmacological properties specifically explored for anticancer effects. The compound is under clinical trials for different types of cancer treatment. Structural modification of genistein has been done to prepare analogs with improved anticancer potential and pharmaceutical properties. Also, novel formulations of genistein have been developed to further improve water solubility and bioavailability for better clinical effectiveness. In the present review, we have summarized the recent available literature on genistein anticancer effects along with mechanism of action and clinical trial studies, reported analogs and novel formulations developed for improving the anticancer efficacy of genistein during the period 2013–2022. Also, the structure activity relationship (SAR) study of reported genistein analogs is described. Further, articles published in this period showed that both genistein and its various derivatives exhibit promising potential for the development of effective chemotherapeutic agents against different types of cancer. Further, the present review will help the researchers in design and development of genistein formulation with desired drug profile.

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Synthesis and Cytotoxicity of 2,3-Enopyranosyl C-Linked Conjugates of Genistein

Cited by 13 publications

References 43 publications

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells

A Small Sugar Molecule with Huge Potential in Targeted Cancer Therapy

Therapeutic Potential of Genistein and its Derivatives as a Target for Anticancer Agents

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