Potent Antagonist for the Vitamin D Receptor: Vitamin D Analogues with Simple Side Chain Structure

2010 ◽  
Vol 53 (15) ◽  
pp. 5813-5826 ◽  
Author(s):  
Yuta Sakamaki ◽  
Yuka Inaba ◽  
Nobuko Yoshimoto ◽  
Keiko Yamamoto
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Chain Structure ◽  
Side Chain ◽  
Vitamin D Analogues ◽  
Potent Antagonist

The First Locked Side-Chain Analogues of Calcitriol (1α,25-Dihydroxyvitamin D3) Induce Vitamin D Receptor Transcriptional Activity

2003 ◽  
Vol 5 (22) ◽  
pp. 4033-4036 ◽  
Author(s):  
Xenxo Pérez-García ◽  
Antonio Rumbo ◽  
María Jesús Larriba ◽  
Paloma Ordóñez ◽  
Alberto Muñoz ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Transcriptional Activity ◽  
Side Chain ◽  
Dihydroxyvitamin D3

Atom-based and Pharmacophore-based 3D – QSAR Studies on Vitamin D Receptor (VDR)

2018 ◽  
Vol 21 (5) ◽  
pp. 329-343 ◽  
Author(s):  
Selvaraman Nagamani ◽  
Chandrasekhar Kesavan ◽  
Karthikeyan Muthusamy
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Binding Free Energy ◽  
3D Qsar ◽  
Free Energy Calculations ◽  
Biologically Active ◽  
Hydroxyl Group ◽  
Qsar Studies ◽  
Vitamin D Analogues ◽  
Semi Empirical

Aim and Objective: Vitamin D3 (1,25(OH)2D3) is a biologically active metabolite and plays a wide variety of regulatory functions in human systems. Currently, several Vitamin D analogues have been synthesized and tested against VDR (Vitamin D Receptor). Electrostatic potential methods are greatly influence the structure-based drug discovery. In this study, ab inito (DFT, HF, LMP2) and semi-empirical (RM1, AM1, PM3, MNDO, MNDO/d) charges were examined on the basis of their concert in predicting the docking pose using Induced Fit Docking (IFD) and binding free energy calculations against the VDR. Materials and Methods: Initially, we applied ab initio and semi-empirical charges to the 38 vitamin D analogues. Further, the charged analogues have been docked in the VDR active site. We generated the structure-based 3D-QSAR from the docked conformation of vitamin D analogues. On the other hand, we performed pharmacophore-based 3D-QSAR. Results: The result shows that, AM1 is the good charge model for our study and AM1 charge based QSAR produced more accurate ligand poses. Furthermore, the hydroxyl group in the side chain of vitamin D analogues played an important role in the VDR antagonistic activity. Conclusion: Overall, we found that charge-based optimizations of ligands were out performed than the pharmacophore based QSAR model.

scholarly journals Carborane-based design of a potent vitamin D receptor agonist

2016 ◽  
Vol 7 (2) ◽  
pp. 1033-1037 ◽  
Author(s):  
Rocio Otero ◽  
Samuel Seoane ◽  
Rita Sigüeiro ◽  
Anna Y. Belorusova ◽  
Miguel A. Maestro ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Receptor Agonist ◽  
Side Chain ◽  
Vitamin D Analog ◽  
Dihydrogen Bonding

The development of a promising clinical antitumor vitamin D analog possessing a side-chain o-carborane cluster that efficiently binds to VDR by unconventional dihydrogen bonding (BH⋯HN) is described.

Design, Synthesis and Evaluation of Side-Chain Hydroxylated Derivatives of Lithocholic Acid as Potent Agonists of the Vitamin D Receptor (VDR)

2021 ◽  
pp. 105202
Author(s):  
Carmen M. González ◽  
Sunil Gaikwad ◽  
Gonzalo Lasanta ◽  
Julian Loureiro ◽  
Niclas Nilsson ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Lithocholic Acid ◽  
Side Chain ◽  
Design Synthesis ◽  
Derivatives Of

ChemInform Abstract: New Synthetic Strategies to Vitamin D Analogues Modified at the Side Chain and D Ring. Synthesis of 1α,25-Dihydroxy-16-ene-vitamin D3 and C-20 Analogues.

ChemInform ◽  
2010 ◽  
Vol 30 (37) ◽  
pp. no-no
Author(s):  
Maria de los Angeles Rey ◽  
Jose Antonio Martinez-Perez ◽  
Ana Fernandez-Gacio ◽  
Koen Halkes ◽  
Yagamare Fall ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Side Chain ◽  
Vitamin D Analogues ◽  
Ring Synthesis

New Synthetic Strategies to Vitamin D Analogues Modified at the Side Chain and D Ring. Synthesis of 1α,25-Dihydroxy-16-ene-vitamin D3and C-20 Analogues1

1999 ◽  
Vol 64 (9) ◽  
pp. 3196-3206 ◽  
Author(s):  
María de los Angeles Rey ◽  
José Antonio Martínez-Pérez ◽  
Ana Fernández-Gacio ◽  
Koen Halkes ◽  
Yagamare Fall ◽  
...  
Keyword(s):  
Vitamin D ◽  
Side Chain ◽  
Vitamin D Analogues ◽  
Ring Synthesis

Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor

2014 ◽  
Vol 57 (10) ◽  
pp. 4073-4087 ◽  
Author(s):  
Takeru Kudo ◽  
Michiyasu Ishizawa ◽  
Kazuki Maekawa ◽  
Makoto Nakabayashi ◽  
Yusuke Watarai ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Triple Bond ◽  
Side Chain ◽  
Partial Agonists

scholarly journals Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

2018 ◽  
Vol 19 (9) ◽  
pp. 2583 ◽  
Author(s):  
Tomasz Wasiewicz ◽  
Anna Piotrowska ◽  
Justyna Wierzbicka ◽  
Andrzej Slominski ◽  
Michal Zmijewski
Keyword(s):  
Vitamin D ◽  
Cell Lines ◽  
Vitamin D Receptor ◽  
Melanoma Cell ◽  
Human Melanoma ◽  
Side Chain ◽  
Short Side ◽  
Vitamin D Analogs ◽  
Splicing Variants ◽  
Melanoma Cell Lines

Vitamin D is a precursor for secosteroidal hormones, which demonstrate pleiotropic biological activities, including the regulation of growth and the differentiation of normal and malignant cells. Our previous studies have indicated that the inhibition of melanoma proliferation by a short side-chain, low calcemic analog of vitamin D—21(OH)pD is not fully dependent on the expression of vitamin D receptor (VDR). We have examined the effects of classic vitamin D metabolites, 1,25(OH)2D3 and 25(OH)D3, and two low calcemic vitamin D analogs, (21(OH)pD and calcipotriol), on proliferation, mRNA expression and vitamin D receptor (VDR) translocation in three human melanoma cell lines: WM98, A375 and SK-MEL-188b (subline b of SK-MEL-188, which lost responsiveness to 1,25(OH)2D3 and became VDR−/−CYP27B1−/−). All tested compounds efficiently inhibited the proliferation of WM98 and A375 melanoma cells except SK-MEL-188b, in which only the short side-chain vitamin D analog—21(OH)pD was effective. Overall, 21(OH)pD was the most potent compound in all three melanoma cell lines in the study. The lack of responsiveness of SK-MEL-188b to 1,25(OH)2D3, 25(OH)D3 and calcipotriol is explained by a lack of characteristic transcripts for the VDR, its splicing variants as well as for vitamin D-activating enzyme CYP27B1. On the other hand, the expression of VDR and its splicing variants and other vitamin D related genes (RXR, PDIA3, CYP3A4, CYP2R1, CYP27B1, CYP24A1 and CYP11A1) was detected in WM98 and A375 melanomas with the transcript levels being modulated by vitamin D analogs. The expression of VDR isoforms in WM98 cells was stimulated strongly by calcipotriol. The antiproliferative activities of 21(OH)pD appear not to require VDR translocation to the nucleus, which explains the high efficacy of this noncalcemic pregnacalciferol analog in SK-MEL-188b melanoma, that is, VDR−/−. Therefore, we propose that 21(OH)pD is a good candidate for melanoma therapy, although the mechanism of its action remains to be defined.

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