Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

Pietraszek, Anita; Malińska, Maura; Chodyński, Michał; Martynow, Jacek; Krupa, Małgorzata; Maruszak, Wioleta; Woźniak, Krzysztof; Kutner, Andrzej

doi:10.1002/jps.23701

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…All of them were analyzed to find packing similarity and hydrogen bond motifs with the aid of the Mercury program . CSD refcodes: EFEHII, EFEHOO, GAJNOX, GAJNUD, HIJFAH, KAKTOH, MIJXUA NAJPOE, NAJPUK, QURJUI, SUJCUX, TEZPIZ, TEZPOF, TEZQAS, WACHIR, WUTVUD, and ZUNFUL (Figure S1, Supporting Information). One of the mentioned analogues HIJFAH (crystal structure of hydrated 1,25D 3 ) was used in computational studies as a reference molecule.…”

Section: Experimental Sectionmentioning

confidence: 99%

“…Until now, the only known examples of the chair α-conformation in the crystal lattice were the monohydrate of (24 R )-1,24-dihydroxyvitamin D 3 (tacalcitol) and 7-methyl-1α,25-(OH) 2 -19- nor -D 3 . Moreover, several examples of vitamin D 3 adopting a chair α-conformation − have been described along with an example of the anhydrous form of calcipotriol also adopting both α- and β-conformations. However, the reasons for these preferences still remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Vitamin D Conformation on Interactions and Packing in the Crystal Lattice

Wanat

Malińska

Kutner

et al. 2018

Crystal Growth & Design

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The crystal and molecular structures of a series of structurally related analogues of 1,25-dihydroxyvitamin D2 and of the first analogue with all hydroxyl groups protected were established with single crystal X-ray structural analysis. With the use of the new structural data, we proposed that the A-ring conformation depends on hydrogen bonding of the hydroxyl groups of the A-ring. The A-ring of the 1α-hydroxylated vitamin D analogues exists in the solid state in a preferred chair β-conformation induced by direct hydrogen bonds between the 1-OH and 3-OH hydroxyl groups. In the same A-ring conformation, the vitamin D analogue interacts with the vitamin D receptor. Indirect hydrogen bonds between the A-ring hydroxyl groups, such as the ones through the water molecule, or hydrogen bonds between the A-ring hydroxyl groups and side-chain hydroxyl groups, induce the α-conformation. Theoretical calculations performed in vacuo showed that the β-form has a slightly lower energy than the α-form. Not only the hydroxyl groups but also the exocyclic methylene highly influences intermolecular interactions including the hydrogen bond pattern in the crystal lattices.

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Section: Experimental Sectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Vitamin D Conformation on Interactions and Packing in the Crystal Lattice

Wanat

Malińska

Kutner

et al. 2018

Crystal Growth & Design

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“…To extend analysis on structures of 1,25(OH) 2 D 3 [ 16 ] and calcipotriol [ 17 ] we transferred the pseudoatom parameters from UBDB2016 [ 29 ] to the major component of molecular structure (the part with the highest occupancy factors for atoms) after elongation of the X-H bond lengths to averaged neutron values. Only this part of the crystal structure was included in further analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Crystal structures of BNR-1, PRI-1730 and PRI-1731 refined with the independent atom model (IAM) were published in our previous work [ 10 ]. Additionally, in this work, we present the analysis of topological properties and electrostatic interactions of 1,25(OH) 2 D 3 [ 16 ] and calcipotriol [ 17 ] as examples of the natural metabolite and the drug substance, respectively.…”

Section: Introductionmentioning

confidence: 99%

First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues

et al. 2022

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Vitamins D are a group of fat-soluble secosteroids which play a regulatory role in the functioning of most cells. Rational design of new vitamin D analogs, of increased therapeutic potency and lowered calcemic side effects, requires high-resolution initial structures and a deep understanding of interactions with the molecular targets. In this paper, using quantum crystallography, we present the first determination of the experimental quantitative charge density of an advanced intermediate of vitamin D analogues as well as a reconstruction of the theoretical electron density of final vitamin D analogues. Application of these methods allows for topological and electrostatic interaction energy analysis. We showed that the A-ring chair conformation has a significant influence on the topological properties of vitamin D compounds. Moreover, the interactions between the CD-ring and side-chain additionally stabilize the crystal structure. These results are supported by our theoretical calculations and previous biological studies.

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“…The following vitamin D analogs were used: calcitriol, PRI-2191, PRI-2201, PRI-2202 and PRI-2205. The synthesis of the analogs PRI-2191 (tacalcitol) and PRI-2201 (calcipotriol) was described elsewhere [ 17 , 22 , 43 , 44 , 45 ]. The samples of the compounds were stored in amber ampoules under argon at −20 °C.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Biological Activity of Diastereomeric and Geometric Analogs of Calcipotriol, PRI-2202 and PRI-2205, Against Human HL-60 Leukemia and MCF-7 Breast Cancer Cells

Milczarek

Chodyński

Filip‐Psurska

et al. 2013

Cancers

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Diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, were synthesized as advanced intermediates from vitamin D C-22 benzothiazoyl sulfones and side-chain aldehydes using our convergent strategy. Calcitriol, calcipotriol (PRI-2201) and tacalcitol (PRI-2191) were used as the reference compounds. Among a series of tested analogs the diastereomeric analog PRI-2202 showed the strongest antiproliferative activity on the human breast cancer cell line MCF-7, whereas the geometric analog PRI-2205 was the weakest. Both analogs were less potent in antiproliferative activity against HL-60 cells compared to the reference compounds. The ability to potentiate antiproliferative effect of cisplatin or doxorubicin against HL-60 cells or that of tamoxifen against the MCF-7 cell line was observed at higher doses of PRI-2202 or PRI-2205 than those of the reference compounds. The proapoptotic activity of tamoxifen, expressed as the diminished mitochondrial membrane potential, as well as the increased phosphatidylserine expression, was partially attenuated by calcitriol, PRI-2191, PRI-2201 and PRI-2205. The treatment of the MCF-7 cells with tamoxifen alone resulted in an increase in VDR expression. Moreover, a further increase in VDR expression was observed when the analogs PRI-2201 or PRI-2205, but not PRI-2191, were used in combination with tamoxifen. This observation could partially explain the potentiation of the antiproliferative effect of tamoxifen by vitamin D analogs.

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Synthesis and Crystal Structure of Anhydrous Analog of 1,25-Dihydroxyvitamin D3

Cited by 7 publications

References 24 publications

Effect of Vitamin D Conformation on Interactions and Packing in the Crystal Lattice

Effect of Vitamin D Conformation on Interactions and Packing in the Crystal Lattice

First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues

Synthesis and Biological Activity of Diastereomeric and Geometric Analogs of Calcipotriol, PRI-2202 and PRI-2205, Against Human HL-60 Leukemia and MCF-7 Breast Cancer Cells

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