Docking, Synthesis, and in vitro Evaluation of Antimitotic Estrone Analogs

Stander, André; Joubert, Fourie; Joubert, Annie M.

doi:10.1111/j.1747-0285.2010.01064.x

Cited by 53 publications

(187 citation statements)

References 49 publications

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“…1a) by modifying the 2′ and 17′ positions with moieties known to improve the anti-mitotic activity and increase the half-life of the compounds [10,11]. This panel was analysed using AutoDockTools4 with the prepare_ligand4py script to determine which compounds bound best with the tubulin colchicine binding site and with carbonic anhydrase IX (CA IX) [10].…”

Section: Introductionmentioning

confidence: 99%

“…This panel was analysed using AutoDockTools4 with the prepare_ligand4py script to determine which compounds bound best with the tubulin colchicine binding site and with carbonic anhydrase IX (CA IX) [10]. CA IX is overexpressed in numerous tumour cells, lending a growth advantage to malignant cells within the acidic and hypoxic microenvironment [12]. Selective inhibition of CA IX could potentially be useful in manipulating the extracellular tumour milieu and curtailing metastatic properties.…”

Section: Introductionmentioning

confidence: 99%

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Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations

Theron

Prudent²,

Nolte

et al. 2014

Cancer Chemother Pharmacol

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overexpressing multidrug-resistant uterine sarcoma cell line. The non-sulphamoylated compounds were only cytotoxic at micromolar ranges, if at all. The sulphamoylated compounds inhibited pure tubulin polymerization in a dose-dependent manner and induced microtubule destruction in cells after 24-h exposure. Conclusion Results revealed that the novel sulphamoylated 2ME derivatives have potential as anti-cancer drugs, possibly even against chemoresistant cancer cells. These compounds disrupt the intracellular microtubule integrity which leads to mitotic block of the cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations

Theron

Prudent²,

Nolte

et al. 2014

Cancer Chemother Pharmacol

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“…Research showed that ESE-16 was an antimitotic compound and induced apoptosis in these cancer cell lines (Stander et al, 2011;Stander et al, 2012;Nkandue et al, 2013;Stander et al, 2013;Theron et al, 2013). It is important to note that ESE-16 has also been tested on nontumorigenic MCF-12 A breast cells and has shown a higher affinity for cancerous cell lines when compared with this noncancerous cell line (Stander et al, 2012;Stander et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Platelets were exposed to 0.18 μM of ESE-16 (Stander et al, 2011). This concentration was selected as it was previously established that 0.18 μM of ESE-16 inhibited cell growth by 50% (GI 50 ) after 24 h at 37°C (Stander et al, 2011;Stander et al, 2012;Stander et al, 2013).…”

Section: Preparation Of Compoundmentioning

confidence: 99%

Ex vivoDetermination of an Estradiol Analogue-Induced Changes on Platelet Morphology and Angiogenic Biomarkers

2015

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Angiogenesis is a closely controlled biological process that takes place during fetal development of blood vessels and wound healing, and includes the development of new blood vessels from preexisting blood vessels. Tumor angiogenesis is a means by which tumors obtain oxygen, nutrition and promote tumor growth. Angiogenesis-regulating proteins are therefore ideal biomarkers in the study of tumor pathophysiology. In our laboratory, a new in silico-designed analogue of 2-methoxyestradiol has been synthesized with angiogenic properties, namely 2-ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16). The ex vivo influence of ESE-16 on angiogenesis and morphology in platelets of healthy participants was investigated. Scanning electron microscopy revealed no morphological changes in ESE-16-treated platelets. The possible antiangiogenic effect of ESE-16-exposed platelets was determined by means of flow cytometry measurement of angiogenic protein levels, which were significantly increased after platelets were added to tumorigenic breast epithelial cells. This indicates that binding of platelets to cancer cells causes differential release of platelet constituents. Vascular endothelial growth factor levels were decreased in platelets, whereas platelet-derived growth factor and matrix metallopeptidase-9 levels were not significantly affected in platelets. In light of the above-mentioned data, further investigation of ESE-16's influence on morphology and angiogenic markers in platelets of cancer patients is warranted.

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“…Inhibitor design based on the estrane core is nonetheless limited, because they must be devoid of estrogenic activity [13][14][15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

Comparative investigation of thein vitroinhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17β-hydroxysteroid dehydrogenase type 1

Herman

Szabó

Bacsa

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17b-hydroxysteroid dehydrogenase type 1 isozyme (17b-HSD1) were investigated. The transformation of estrone to 17b-estradiol was studied by an in vitro radiosubstrate incubation method. 13a-Estrone inhibited the enzyme activity effectively with an IC 50 value of 1.2 mM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13b derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13a and 3-ether counterparts. The 3-hydroxy13b-D-secoalcohol and the 3-hydroxy-13a-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy13b-D-secooxime has an IC 50 value of 0.070 mM and is one of the most effective 17b-HSD1 inhibitors reported to date in the literature.

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Docking, Synthesis, and in vitro Evaluation of Antimitotic Estrone Analogs

Cited by 53 publications

References 49 publications

Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations

Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations

Ex vivoDetermination of an Estradiol Analogue-Induced Changes on Platelet Morphology and Angiogenic Biomarkers

Comparative investigation of thein vitroinhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17β-hydroxysteroid dehydrogenase type 1

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