Structure–activity study of retinoid agonists bearing substituted dicarba-closo-dodecaborane. Relation between retinoidal activity and conformation of two aromatic nuclei

Endo, Yasuyuki; Iijima, Toru; Yaguchi, Kyoko; Kawachi, Emiko; Inoue, Noriko; Kagechika, Hiroyuki; Kubo, Asako; Itai, Akiko

doi:10.1016/s0960-894x(01)00204-9

Cited by 44 publications

(38 citation statements)

References 26 publications

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“…The tetrahydronaphthalene derivative group of QT-011 acted as the hydrophobic region of the molecule, which fit well with the hydrophobic pocket of the RARs (Ile112, Leu268, Phe230, Trp227, Phe304, Leu307, Leu416, and Ala397). These results are consistent with the study of Yasuyuki (Endo et al, 2001). In addition, three hydrogen bonds were observed between the remainder of the QT-011 and the Thr200, Arg274, and Ser289 of RARs.…”

Section: Docking Of Qt-011 With Rarsupporting

confidence: 93%

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Wang¹,

Duan²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.

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Section: Docking Of Qt-011 With Rarsupporting

confidence: 93%

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Wang¹,

Duan²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…[3][4][5] We have reported applications of carboranes in medicinal drug design as a hydrophobic component of biologically active molecules, 6) targeting nuclear receptors, such as estrogen receptor (ER), 7,8) androgen receptor (AR), 9,10) retinoic acid receptor (RAR) 11,12) and retinoid X receptor (RXR).…”

Section: Notesmentioning

confidence: 99%

“…1,2) Biomedical applications of the carboranes, e.g., in boron neutron capture therapy (BNCT), are of great interest. [3][4][5] We have reported applications of carboranes in medicinal drug design as a hydrophobic component of biologically active molecules, 6) targeting nuclear receptors, such as estrogen receptor (ER), 7,8) androgen receptor (AR), 9,10) retinoic acid receptor (RAR) 11,12) and retinoid X receptor (RXR). 13) It was suggested that the carborane cage works as a hydrophobic group for binding to the hydrophobic cavity of the ligand-binding domain (LBD) on the nuclear receptors, and that hydrophobic van der Waals contacts along the spherical carborane cage produce a stronger interaction than that in the case of the native ligand.…”

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confidence: 99%

Complexation of .ALPHA.-Cyclodextrin with Carborane Derivatives in Aqueous Solution

Ohta

Konno

Endo

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesIcosahedral carboranes (dicarba-closo-dodecaboranes) have unique structural and chemical properties, such as high boron content, spherical structure, three isomers (ortho, meta and para), a highly hydrophobic surface, and unexpected thermal and chemical stability (Fig. 1).1,2) Biomedical applications of the carboranes, e.g., in boron neutron capture therapy (BNCT), are of great interest. [3][4][5] We have reported applications of carboranes in medicinal drug design as a hydrophobic component of biologically active molecules, 6) targeting nuclear receptors, such as estrogen receptor (ER), 7,8) androgen receptor (AR), 9,10) retinoic acid receptor (RAR) 11,12) and retinoid X receptor (RXR).13) It was suggested that the carborane cage works as a hydrophobic group for binding to the hydrophobic cavity of the ligand-binding domain (LBD) on the nuclear receptors, and that hydrophobic van der Waals contacts along the spherical carborane cage produce a stronger interaction than that in the case of the native ligand. In the development of carborane-containing estrogen ligands, we have investigated the hydrophobicity of carboranes by measuring the partition coefficients, log P values, and the hydrophobicity parameter p. 14,15) Cyclodextrins (CDs) are widely used as host molecules in a number of areas of chemistry where molecular recognition is required, such as material sciences, supramolecular chemistry, molecular-sensing, and artificial enzymes (Fig. 1). Moreover, CDs are of great utility in the field of medicinal chemistry as solubilizing agents for lipophilic drugs, [16][17][18] as photostabilizers of light-sensitive drugs, [19][20][21] and as sustained-release [16][17][18] and drug delivery systems [22][23][24] for various drugs.Complexes of a-, b-, and g-CD with unsubstituted ocarborane (1a) were isolated, and the stoichiometries of the complexes were determined by elemental analysis and from the ratios of the 1 H-NMR peaks.25) However, the stoichiometric ratio, association constant and complex formation in solution have not been well characterized. Recently, Threadgill and co-workers have reported the formation of a remarkably robust 2 : 1 complex of b-CD with 1-phenyl-o-carborane. 26)An excellent fit of the carborane cage with b-CD was confirmed by a molecular modelling study. This work dealt only with the o-carborane isomer. The attractive properties of mand p-carboranes 27) mean that complexation of these molecules with CDs is also of interest. It is noteworthy that b-CDbonded chiral stationary phases have been used for enantiomeric resolution in the ten-vertex carborane series, 28,29) implying a strong interaction of ten-vertex carborane with b-CD.However, the host-guest complexations of carboranes with CDs are not well understood. Therefore, we have focused on the interaction between the spherical, hydrophobic surface of carboranes and the hydrophobic pocket of CDs. Recently, we reported the complexation of carborane derivatives with b-CD, including association constant values and stoichiometry in aqueous ...

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“…[45,46] There are many examples of closo-carboranes having been used as bioisosteric replacements for heteroaromatic or heteroaliphatic rings. [47][48][49][50][51][52][53][54][55][56] Due to the complexity of substituting each individual boron atom within the carborane cluster with carbon atoms, we considered an alternative approach, where the entire carborane cluster is replaced with a simple phenyl ring for molecular docking experiments, given the similar 3D sweep volume and high lipophilicity of both moieties.…”

Section: Resultsmentioning

confidence: 99%

Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT)

et al. 2020

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Based on the previously reported potent and selective sulfone hydroxamate inhibitors SC-76276, SC-78080 (SD-2590), and SC-77964, potent MMP inhibitors have been designed and synthesized to append a boron-rich carborane cluster by employing click chemistry to target tumor cells that are known to upregulate gelatinases. Docking against MMP-2 suggests binding involving the hydroxamate zinc-binding group, key Hbonds by the sulfone moiety with the peptide backbone residues Leu82 and Leu83, and a hydrophobic interaction with the deep P1' pocket. The more potent of the two triazole regioisomers exhibits an IC 50 of 3.7 nM versus MMP-2 and IC 50 of 46 nM versus MMP-9.

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Structure–activity study of retinoid agonists bearing substituted dicarba-closo-dodecaborane. Relation between retinoidal activity and conformation of two aromatic nuclei

Cited by 44 publications

References 26 publications

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative

Complexation of .ALPHA.-Cyclodextrin with Carborane Derivatives in Aqueous Solution

Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT)

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