3D-QSAR Studies on C24-Monoalkylated Vitamin D3 26,23-Lactones and their C2α-Modified Derivatives with Inhibitory Activity to Vitamin D Receptor

2010 ◽  
Vol 29 (8-9) ◽  
pp. 621-632 ◽  
Author(s):  
Jinhu Wang ◽  
Ke Tang ◽  
Qianqian Hou ◽  
Xueli Cheng ◽  
Lihua Dong ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Inhibitory Activity ◽  
3D Qsar ◽  
Qsar Studies

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.

3D QSAR Studies of Tricyclic Compounds as Porcupine Inhibitors for Wnt Pathway Inhibitory Activity

2018 ◽  
Vol 15 (7) ◽  
pp. 721-732
Author(s):  
Liqiang Meng ◽  
Liqian Sun ◽  
Chaoqun Yan ◽  
Dongxiao Cui ◽  
Jingrun Chen ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Wnt Pathway ◽  
3D Qsar ◽  
Qsar Studies ◽  
Tricyclic Compounds

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors

2021 ◽  
pp. 1-14
Author(s):  
Elham Kazemian ◽  
Sayed Hossein Davoodi ◽  
Mohammad Esmaeil Akbari ◽  
Nariman Moradi ◽  
Safoora Gharibzadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Cancer Survivors ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Breast Cancer Survivors ◽  
Allelic Variants ◽  
Vitamin D3 Supplementation

Identification of a highly potent vitamin D receptor antagonist: (25S)-26-Adamantyl-25-hydroxy-2-methylene-22,23-didehydro-19,27-dinor-20-epi-vitamin D3 (ADMI3)

2007 ◽  
Vol 460 (2) ◽  
pp. 240-253 ◽  
Author(s):  
Miharu Igarashi ◽  
Nobuko Yoshimoto ◽  
Keiko Yamamoto ◽  
Masato Shimizu ◽  
Michiyasu Ishizawa ◽  
...  
Keyword(s):  
Vitamin D ◽  
Receptor Antagonist ◽  
Vitamin D Receptor ◽  
Vitamin D3

scholarly journals A Positive GATA Element and a Negative Vitamin D Receptor-Like Element Control Atrial Chamber-Specific Expression of a Slow Myosin Heavy-Chain Gene during Cardiac Morphogenesis

1998 ◽  
Vol 18 (10) ◽  
pp. 6023-6034 ◽  
Author(s):  
Gang Feng Wang ◽  
William Nikovits ◽  
Mark Schleinitz ◽  
Frank E. Stockdale
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Heavy Chain ◽  
Inhibitory Activity ◽  
Binding Motif ◽  
Specific Expression ◽  
Ventricular Cardiomyocytes ◽  
Slow Myosin Heavy Chain ◽  
Slow Myhc

ABSTRACT We have used the slow myosin heavy chain (MyHC) 3 gene to study the molecular mechanisms that control atrial chamber-specific gene expression. Initially, slow MyHC 3 is uniformly expressed throughout the tubular heart of the quail embryo. As cardiac development proceeds, an anterior-posterior gradient of slow MyHC 3 expression develops, culminating in atrial chamber-restricted expression of this gene following chamberization. Two cis elements within the slow MyHC 3 gene promoter, a GATA-binding motif and a vitamin D receptor (VDR)-like binding motif, control chamber-specific expression. The GATA element of the slow MyHC 3 is sufficient for expression of a heterologous reporter gene in both atrial and ventricular cardiomyocytes, and expression of GATA-4, but not Nkx2-5 or myocyte enhancer factor 2C, activates reporter gene expression in fibroblasts. Equivalent levels of GATA-binding activity were found in extracts of atrial and ventricular cardiomyocytes from embryonic chamberized hearts. These observations suggest that GATA factors positively regulate slow MyHC 3 gene expression throughout the tubular heart and subsequently in the atria. In contrast, an inhibitory activity, operating through the VDR-like element, increased in ventricular cardiomyocytes during the transition of the heart from a tubular to a chambered structure. Overexpression of the VDR, acting via the VDR-like element, duplicates the inhibitory activity in ventricular but not in atrial cardiomyocytes. These data suggest that atrial chamber-specific expression of the slow MyHC 3 gene is achieved through the VDR-like inhibitory element in ventricular cardiomyocytes at the time distinct atrial and ventricular chambers form.

Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore

2005 ◽  
Vol 40 (10) ◽  
pp. 977-990 ◽  
Author(s):  
Sunil K. Singh ◽  
V. Saibaba ◽  
K. Srinivasa Rao ◽  
P. Ganapati Reddy ◽  
Pankaj R. Daga ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
3D Qsar ◽  
Qsar Studies ◽  
Cox 2

scholarly journals Vitamin D3 induces vitamin D receptor and HDAC11 binding to relieve the promoter of the tight junction proteins

Oncotarget ◽  
2017 ◽  
Vol 8 (35) ◽  
pp. 58781-58789 ◽  
Author(s):  
Feng-Hua Liu ◽  
Shan-Shan Li ◽  
Xiao-Xi Li ◽  
Shuai Wang ◽  
Mao-Gang Li ◽  
...  
Keyword(s):  
Vitamin D ◽  
Tight Junction ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Tight Junction Proteins ◽  
Junction Proteins

scholarly journals 25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism

2019 ◽  
Vol 20 (9) ◽  
pp. 2367 ◽  
Author(s):  
Amiram Ravid ◽  
Noa Rapaport ◽  
Assaf Issachar ◽  
Arie Erman ◽  
Larisa Bachmetov ◽  
...  
Keyword(s):  
Vitamin D ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Mode Of Action ◽  
Virus Production ◽  
Independent Manner ◽  
Hydroxyvitamin D ◽  
Independent Mechanism

Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3β-hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.

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