Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines

Jorda, Radek; Řezníčková, Eva; Kiełczewska, Urszula; Maj, Jadwiga; Morzycki, Jacek W.; Siergiejczyk, Leszek; Bazgier, Václav; Berka, Karel; Rárová, Lucie; Wojtkielewicz, Agnieszka

doi:10.1016/j.ejmech.2019.06.040

Cited by 21 publications

(12 citation statements)

References 16 publications

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“…The target galeterone derivatives were obtained in good yields by heating under reflux in dry MeCN in the presence of p-TsOH (Scheme 17). 60 Under these conditions, in addition to the predominant aromatic products 60a-c, 60'c, D-homo-ketones 61a-c, 61'c were obtained which were formed as autoxidation products. In addition, from the mixture of derivatives 60c, 60'c and 61c, 61'c, the regioisomers were isolated as individual products.…”

Section: Scheme 12mentioning

confidence: 97%

“…The values of the maximum inhibition 11). 60 Pyrimidobenzimidazole derivatives 70, 71 a-h 65 showed antibacterial activity with a MIC of 2 μg/ml against Grampositive bacteria and 1 μg/ml against Gram-negative bacteria. Compounds 70, 71 a-h showed antibacterial activity superior to ciprofloxacin against Enterococcus faecalis with a MIC of 0.2 to 0.8 μg/ml.…”

Section: Biological Activity Of Pyrimidobenzimidazole Derivativesmentioning

confidence: 99%

“…The values of the maximum inhibition of cell proliferation (GI 50 ) of compounds 60a – c , 60'c , 61a – c , and 60”a lie in the middle micromolar range (Table 11 ). 60 …”

Section: Biological Activity Of Pyrimidobenzimidazole Derivativesmentioning

confidence: 99%

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Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

Fedotov

Русинов

Ulomsky

et al. 2021

Chem Heterocycl Comp

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Nitrogen-containing heterocyclic compounds are the basis of many natural and synthetic biologically active substances. 1 More than two-thirds of the known drugs used in clinical practice contain heterocyclic and, above all, nitrogen-containing fragments within their structure. Over the past decades, the chemistry of aza-heterocycles has received considerable attention due to the wide spectrum of their biological activity and numerous therapeutic applications in medicine.Of nitrogenous heterocycles, azoloazines containing fragments similar to the natural heterocycles purines and pyrimidines are currently of great practical importance. Thus, non-natural nucleosides abacavir, famciclovir, remdesivir are known, which are the products of structural modifications of all the components of the nucleotide exhibiting excellent indicators of antiviral action (Fig. 1). [2][3][4] In addition to the generally accepted nucleoside forms, the azoloazines themselves are relevant in the search for means of combating diseases on a global scale. Nitroazolo- [5,1-c][1,2,4]triazines and nitroazolo [1,5-a]pyrimidines, a new family of antiviral compounds has been found. 5 The

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Section: Scheme 12mentioning

confidence: 97%

Section: Biological Activity Of Pyrimidobenzimidazole Derivativesmentioning

confidence: 99%

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Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

Fedotov

Русинов

Ulomsky

et al. 2021

Chem Heterocycl Comp

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“…Androgen receptors and related signal pathways play an important role in prostate cancer cell proliferation and are the main target of androgen‐deprivation therapy [1]. Basic principles of prostate cancer therapy are using of androgen biosynthesis inhibitors (such as abiraterone), as well as androgen receptor antagonists (such as enzalutamide), and androgen receptor degraders [2–4]. It is known that prostate cancer cells are capable to express both full‐length androgen receptor and aberrant splicing forms of the receptor, including AR‐V7, associated with unfavorable outcome of the disease and resistance to abiraterone and enzalutamide [1–3].…”

Section: Introductionmentioning

confidence: 99%

“…Galeterone was also speculated to have higher selectivity toward 17,20‐lyase activity of CYP17A1 than abiraterone, which was indirectly confirmed by relatively small increase in corticosterone level in patients after galeterone administration for 12 weeks, compared to that of after therapy with abiraterone [7]. Despite clinical trials of galeterone being on hold, it was shown that the use of galeterone and its derivatives is a potentially effective therapeutic strategy for castrate‐resistant prostate cancer patients with found androgen receptor splice form AR‐V7 [1,3,8].…”

Section: Introductionmentioning

confidence: 99%

Interactions of galeterone and its 3‐keto‐Δ4 metabolite (D4G) with one of the key enzymes of corticosteroid biosynthesis – steroid 21‐monooxygenase (CYP21A2)

Masamrekh

Filippova

Sherbakov

et al. 2020

Fundamemntal Clinical Pharma

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We have investigated interactions of galeterone and its pharmacologically active metabolite – 3‐keto‐Δ4‐galeterone (D4G) – with one of the key enzymes of corticosteroid biosynthesis – steroid 21‐monooxygenase (CYP21A2). It was shown by absorption spectroscopy that both compounds induce type I spectral changes of CYP21A2. Spectral dissociation constants (KS) of complexes of CYP21A2 with galeterone or D4G were calculated as 3.1 ± 0.7 μm and 4.6 ± 0.4 μm, respectively. It was predicted by molecular docking that both ligands similarly bind to the active site of CYP21A2. We have revealed using reconstituted monooxygenase system that galeterone is a competitive inhibitor of CYP21A2 with the inhibition constant (Ki) value of 12 ± 3 μm, while D4G at the concentrations of 10 and 25 μm does not inhibit the enzyme. Summarizing, based on the in vitro analyses we detected inhibition of CYP21A2 by galeterone and lack of the influence of D4G on this enzyme.

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Isolation and Bioactivity Evaluation of Sesquiterpenes from an Alcyonarian of the Genus Lemnalia from the Saudi Arabian Red Sea

Koutsaviti,

Kvasnicová,

Gonzalez

et al. 2024

Chemistry & Biodiversity

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Over the last decades, soft corals have been proven a rich source of biologically active compounds, featuring a wide range of chemical structures. Herein, we investigated the chemistry of an alcyonarian of the genus Lemnalia (Neptheidae), specimens of which were collected from the coral reefs near Al Lith, on the south‐west coast of Saudi Arabia. A series of chromatographic separations led to the isolation of 31 sesquiterpenes, featuring mainly the nardosinane and neolemnane carbon skeletons, among which three (13, 14 and 28) are new natural products. The metabolites isolated in sufficient amounts were evaluated in vitro in human tumor and non‐cancerous cell lines for a number of biological activities, including their cytotoxic, anti‐inflammatory, anti‐angiogenic, and neuroprotective activities, as well as for their effect on androgen receptor (AR)‐regulated transcription. Among the tested metabolites, compound 12 showed comparable neuroprotective activity to the positive control N‐acetylcysteine, albeit at a 10‐fold lower concentration.

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Synthesis of novel galeterone derivatives and evaluation of their in vitro activity against prostate cancer cell lines

Cited by 21 publications

References 16 publications

Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

Interactions of galeterone and its 3‐keto‐Δ4 metabolite (D4G) with one of the key enzymes of corticosteroid biosynthesis – steroid 21‐monooxygenase (CYP21A2)

Isolation and Bioactivity Evaluation of Sesquiterpenes from an Alcyonarian of the Genus Lemnalia from the Saudi Arabian Red Sea

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