Discovery of Carboranes as Inducers of 20S Proteasome Activity

Ban, Hyun Seung; Minegishi, Hidemitsu; Shimizu, Kazuki; Maruyama, Minako; Yasui, Yuka; Nakamura, Hiroyuki

doi:10.1002/cmdc.201000112

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…Compounds used in this study were synthesized using literature methods [18–24] or as described below. In each case the compounds were purified by flash chromatography or preparative thin layer chromatography.…”

Section: Methodsmentioning

confidence: 99%

Structure–Activity Relationships of Organofluorine Inhibitors of β‐Amyloid Self‐Assembly

et al. 2012

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A broad group of structurally diverse small organofluorine inhibitors have been synthesized and evaluated in the self-assembly of amyloid β. The major goal was to generate a diverse library of compounds with the same functional group and observe general structural features that characterize the oligomer and fibril inhibitors, and ultimately find lead structures for further, focused inhibitor design. The common structural motifs in these compounds were the CF3-C-OH or CF3-C-NH groups that were proposed to be a binding unit in our earlier studies. A broad range of potential small molecule inhibitors were synthesized by adding different carbocyclic and heteroaromatic rings with an array of substituents, overall 106 molecules. The compounds were tested by standard methods, such as thioflavine T-fluorescence spectroscopy for following fibril formation, biotinyl-Aβ(1–42) single-site streptavidin-based assay for observing oligomer formation and atomic force microscopy for morphological studies. These assays yielded a number of structures that showed significant inhibition against either fibril or oligomer formation. A detailed analysis on the structure activity relationship of anti-fibril and -oligomer properties is provided. In addition, these data present further experimental evidence for the distinct nature of the fibril vs oligomer formation and that the interaction of the Aβ peptide with chiral small molecules is not stereospecific in nature.

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Section: Methodsmentioning

confidence: 99%

Structure–Activity Relationships of Organofluorine Inhibitors of β‐Amyloid Self‐Assembly

et al. 2012

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“…The highest antiplatelet aggregation activity of BAA/OAA mixture could be attributed to the modification of hydroxyl moiety at C3 position with acetyl group. Targeting of carbon positions 3 and 28 of compounds are the new pharmacophores to enhance biological activities [19]. It is worth noting that aspirin, a potent antithrombin agent has acetyl moiety as its major functional group [20].…”

Section: Discussionmentioning

confidence: 99%

Anti-platelet aggregation of mixtures of betulinic oleanolic and maslinic acids and derivatives from medicinal plants

Osunsanmi¹,

Oyinloye²,

Mosa³

et al. 2016

Trop. J. Pharm Res

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“…33) They were treated with n-butyl lithium to obtain the lithium salts, which were transformed into copper salts with Cu(I) Cl, and converted to the diaryl-m-carboranes 10a and b in 37% and 39% yields, respectively. 34,35) B-n-Propyl derivative 5a was synthesized by catalytic hydrogenation of the allyl group of 10a, followed by deprotection of the phenol group with BBr 3 in 45% yield over The ER binding affinities of the synthesized compounds were evaluated by means of competitive ER binding assays using [2,4,6, H]17β-estradiol and human recombinant ERα and ERβ. 36) Table 1 summarized the relative binding affinity (RBA) values, estimated based on the RBA of estradiol 2, taken as 100.…”

Section: )mentioning

confidence: 99%

“…2,3) Prior to that, carboranes had been used only as boron carriers for boron neutron capture therapy (BNCT), based on their high boron content. 4) We also designed and synthesized various carborane-containing bioactive compounds as candidate nuclear receptor ligands.…”

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confidence: 99%

Aliphatic Substitution of <i>o</i>-Carboranyl Phenols Enhances Estrogen Receptor Beta Selectivity

Ohta

Ogawa

Kaise

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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The two subtypes of estrogen receptor (ER), ERα and ERβ, differ greatly in expression pattern and biological functions, and ERβ-selective ligands candidates to treat immune-related disorders. ERβ-selective ligands have mostly been designed based the idea of introducing a substituent that interferes sterically with the ligand's interaction with Met421 to selectively decrease the affinity for ERα (the equivalent residue in ERβ is Ile373). Therefore, we designed and synthesized a series of carboranyl phenol derivatives bearing an aliphatic substituent as candidate ERβ-selective ligands. Introduction of a longer aliphatic substituent into the carboranyl moiety enhanced the ERβ selectivity of o-carboranyl phenol derivatives 4, but not m-carboranyl bisphenol derivatives 5. Compound 4c showed 7.4-fold ERβ selectivity in ER-binding assay and exhibited moderate estrogenic activity in cell proliferation assay using MCF-7 cell line.

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Discovery of Carboranes as Inducers of 20S Proteasome Activity

Cited by 18 publications

References 27 publications

Structure–Activity Relationships of Organofluorine Inhibitors of β‐Amyloid Self‐Assembly

Structure–Activity Relationships of Organofluorine Inhibitors of β‐Amyloid Self‐Assembly

Anti-platelet aggregation of mixtures of betulinic oleanolic and maslinic acids and derivatives from medicinal plants

Aliphatic Substitution of <i>o</i>-Carboranyl Phenols Enhances Estrogen Receptor Beta Selectivity

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