A focused library synthesis and cytotoxicity of quinones derived from the natural product bolinaquinone

Ghods, Azadeh; Gilbert, Jayne; Baker, Jennifer R.; Russell, Cecilia C.; Sakoff, Jennette A.; McCluskey, Adam

doi:10.1098/rsos.171189

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…It has previously been hypothesized that natural products can oxidize during in vitro metabolism and are able to form quinones [ 67 , 68 ]. Even more interesting is that quinones have been documented to promote anticancer activity [ 67 , 69 , 70 ]. Considering the prevalence of hydroxyl groups on many mangosteen xanthones structures’, with three hydroxyl groups present on α-mangostin, it could be that a hydroxyl is oxidized and becomes available to bind to one of the two cysteine residues on BiP, which readily bind with quinones [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells

Nauman

Won

Petiwala

et al. 2023

Cancers

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A major limitation of current prostate cancer pharmacotherapy approaches is the inability of these compounds to target androgen receptor variants or mutants that develop during prostate cancer progression. The demand for novel therapeutics to prevent, slow, and treat prostate cancer is significant because FDA approved anti-androgens are associated with adverse events and can eventually drive drug-resistant prostate cancer. This study evaluated α-mangostin for its novel ability to degrade the androgen receptor and androgen receptor variants. α-Mangostin is one of more than 70 isoprenylated xanthones isolated from Garcinia mangostana that we have been evaluating for their anticancer potential. Prostate cancer cells treated with α-mangostin exhibited decreased levels of wild-type and mutated androgen receptors. Immunoblot, immunoprecipitation, and transfection experiments demonstrated that the androgen receptor was ubiquitinated and subsequently degraded via the proteasome, which we hypothesize occurs with the assistance of BiP, an ER chaperone protein that we have shown to associate with the androgen receptor. We also evaluated α-mangostin for its antitumor activity and promotion of androgen receptor degradation in vivo. In summary, our study demonstrates that androgen receptor degradation occurs through the novel activation of BiP and suggests a new therapeutic approach for prostate cancer.

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Section: Discussionmentioning

confidence: 99%

α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells

Nauman

Won

Petiwala

et al. 2023

Cancers

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“…This site was suggested by a molecular dynamics investigation of the potential binding poses of the marine sesquiterpenoid, bolinaquinone. In a protein-pull down experiment, bolinaquinone was reported as a specific inhibitor of clathrin (Abdel-Hamid and McCluskey, 2014 ; Ghods et al, 2018 ).…”

Section: Clathrin—structure and Functionmentioning

confidence: 99%

Role of Clathrin and Dynamin in Clathrin Mediated Endocytosis/Synaptic Vesicle Recycling and Implications in Neurological Diseases

Prichard

O'Brien²,

Murcia³

et al. 2022

Front. Cell. Neurosci.

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Endocytosis is a process essential to the health and well-being of cell. It is required for the internalisation and sorting of “cargo”—the macromolecules, proteins, receptors and lipids of cell signalling. Clathrin mediated endocytosis (CME) is one of the key processes required for cellular well-being and signalling pathway activation. CME is key role to the recycling of synaptic vesicles [synaptic vesicle recycling (SVR)] in the brain, it is pivotal to signalling across synapses enabling intracellular communication in the sensory and nervous systems. In this review we provide an overview of the general process of CME with a particular focus on two key proteins: clathrin and dynamin that have a central role to play in ensuing successful completion of CME. We examine these two proteins as they are the two endocytotic proteins for which small molecule inhibitors, often of known mechanism of action, have been identified. Inhibition of CME offers the potential to develop therapeutic interventions into conditions involving defects in CME. This review will discuss the roles and the current scope of inhibitors of clathrin and dynamin, providing an insight into how further developments could affect neurological disease treatments.

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“…The optimised conditions for the two couplings (38 % over two steps, Table 2, Entry 1) were adapted to a one-pot procedure (Table 2, Entry 2) to afford a more user-friendly procedure. [19] After completion of the first coupling [14 a, PdCl 2 (dppf), K 2 CO 3 , toluene, 120 °C, 24 h], 14 b and CsF were added. Even if symmetrical quinones 16 c and 16 i were also isolated as side products (20 % and 22 % respectively), this sequential loading of boronic acids allowed the formation of the targeted product 16 e with same yield (38 %).…”

Section: Introductionmentioning

confidence: 99%

“…Inspired by Hu [15] and Grée [16] results, we applied sequential Suzuki‐Miyaura couplings on 2,5‐dibromo‐3,6‐dimethoxy‐quinone 12 (Scheme 1). [17–19] They had already found that PdCl 2 (dppf) is the best catalyst to promote Suzuki‐Miyaura couplings on 12 . To ensure a good selectivity of the first Suzuki‐Miyaura coupling and thus the synthetic sequence, we evaluated the effect of the solvent (Table 1, Entries 1‐4) and of the base (K 2 CO 3 or CsF) (Entries 1 & 5) for the coupling of 4‐methoxyphenyl)boronic acid 14 a .…”

Section: Introductionmentioning

confidence: 99%

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Bioinspired Synthesis of Pulvinic Acids Including Xerocomic Acid and Fluorescence Properties of Bis‐lactone Intermediates

et al. 2023

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A set of representative pulvinic acids were synthesised using a bioinspired strategy. Terphenyl‐quinones (polyporic acid scaffold) were prepared via sequential Suzuki‐Miyaura couplings allowing access to unsymmetrically substituted derivatives in a one‐pot protocol. Subjected to the action of acetic anhydride and DMSO, quinones were converted into bis‐lactone intermediates. Methanolysis and deprotection achieved the total syntheses of the corresponding pulvinic acids. Following this general strategy, symmetrical pulvinic, atromentic, variegatic acids and unsymmetrical congener pinastric, iso‐pinastric, xerocomic and iso‐xerocomic acids were prepared in fair yields. Fluorescence properties were observed for the bis‐lactone intermediates and, as a complement to this synthetic work, optical properties were measured, and fluorescence quantum yields were determined for the bis‐lactone pigments.

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A focused library synthesis and cytotoxicity of quinones derived from the natural product bolinaquinone

Cited by 9 publications

References 43 publications

α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells

α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells

Role of Clathrin and Dynamin in Clathrin Mediated Endocytosis/Synaptic Vesicle Recycling and Implications in Neurological Diseases

Bioinspired Synthesis of Pulvinic Acids Including Xerocomic Acid and Fluorescence Properties of Bis‐lactone Intermediates

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