Structure-activity relationship studies of retinoid cancer inhibition

Jaeger, EP; Jurs, P. C.; Stouch, T R

doi:10.1016/0223-5234(93)90145-5

Cited by 18 publications

(10 citation statements)

References 27 publications

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“…1,2 Currently, a lot of interest is being focused on how to understand the role of retinoic acid in cell differentiation. This is done by investigating the binding properties of retinoids on specific proteins, 3,4 its role in malignant-tumor inhibition, 5,6 and its regulation of brain functions. 7 Natural retinoids need to be bound to specific retinoic-binding proteins to ensure their protection, solubility, and transport by body fluids.…”

Section: Introductionmentioning

confidence: 99%

Immobilization of Retinoic Acid by Polyamino Acids: Lamellar-Structured Nanoparticles

Thünemann

Beyermann

Ferber³

et al. 1999

Langmuir

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We discuss the preparation, the X-ray spectra and their theory, and electron microscopy of nanoparticles showing a lamellar internal structure. Retinoic acid was immobilized by complexation with poly(L-arginine), poly(L-histidine), and poly(L-lysine). The resulting solid-state complexes were prepared as nanoparticles with diameters of 320-380 nm, and with internal structures, which are smectic A-like. By small-angle X-ray scattering the unit cell was determined to be in the range of 3.10-3.62 nm, thus depending linearly on the monomer mass. The X-ray scattering of finite lamellar structures of "onion"-and "tart"-type spherical nanoparticles were determined theoretically. The uniform boundary of the onion-type particles results in secondary maxima near the Bragg reflections. Further, the highest degree of polydispersity to find these secondary maxima in scattering experiments was determined to be about 1% if the particle size is 300 nm. When electron microscopy was used, it was shown that the particles consist of a complex-containing core surrounded by a dispersing agent-containing shell. The core was revealed to be more of the tart-than the onion-type. When circular dichroism was used, the conformation of poly(L-arginine) and poly(L-lysine) within the complexes was determined to be an R-helix, whereas that of poly(L-histidine) was predominantly of the coil-type.

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Section: Introductionmentioning

confidence: 99%

Immobilization of Retinoic Acid by Polyamino Acids: Lamellar-Structured Nanoparticles

Thünemann

Beyermann

Ferber³

et al. 1999

Langmuir

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“…The class prediction of known molecules in the validation phase generally agrees well with their experimental af®nity class. Comparisons of the results presented here with those previously published by Bonchev et al [34,35] or Jaeger et al [36] are not straightforward since the earlier studies concerned a QSAR using anticarcinogenic activity and did not take account of RAR subtypes.…”

Section: Discussionmentioning

confidence: 60%

Quantitative structure-activity relationship studies of RAR α, β, γ retinoid agonists

Douguet¹,

Thoreau²,

Grassy³

1999

Quant. Struct.-Act. Relat.

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Structure-Activity Relationships have been established for 140 synthetic retinoid agonists. Retinoids, natural and synthetic analogues of vitamin A, are activating ligands for Retinoic Acid Receptors (RARa, b and g), members of the nuclear receptor superfamily. A QSAR study provides information on the type of intermolecular and intramolecular interactions the active molecules are exposed to during the course of their interaction with the receptor. Retinoid structures were modelled both by molecular and quantum mechanics and were submitted to a preliminary conformational analysis based on molecular dynamics. Linear and non-linear multivariate analyses were performed, revealing the principal electronic and structural characteristics leading to good af®nity for each RAR subtype. Distinct structural features were found for each subtype: this is in agreement with the fact that the selectivity of the RAR subtypes results from the change of amino acids in the ligand cavity. Indeed, these amino-acids induce subtle changes in terms of steric properties and speci®c interactions, thus engendering speci®city. The predictive ability of these relationships has been validated using a large set of compounds which were not used to derive the model. The goal this of work was to detect relationships between structures and af®nity for a broad range of retinoids in order that this model could be used in a more general manner, for example to impose constraints in database searching, or for use in automatic structure generation software.

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“…Currently it is used in the external therapy of serious cases of acne, and it is discussed for use in skin rejuvenation therapy . Further, there have been reports on malignant-tumor inhibition by retinoids. , …”

Section: Introductionmentioning

confidence: 99%

“…4 Further, there have been reports on malignant-tumor inhibition by retinoids. 5,6 All retinoids possess the same characteristic highly UV active chromophor and are hardly soluble as well as chemically unstable in aqueous media. Therefore, natural retinoids need to be bound to specific retinoic-binding proteins in order to allow protection, solubilization, and transport in body fluids.…”

Section: Introductionmentioning

confidence: 99%

Immobilization of Retinoic Acid by Cationic Polyelectrolytes

Thünemann

1997

Langmuir

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Retinoic acid was immobilized by precipitating its complexes with cationic polyelectrolytes from aqueous solution. Polyelectrolytes with different architectures, such as poly(ionene-6,3 bromide), poly(dimethyldiallylammonium chloride), and poly(N-methyl-4-vinylpyridinium chloride), form self-assembling complexes containing retinoic acid (70% (w/w)). All these complexes are thermodynamically stable and can be processed into mesomorphously ordered films with interesting physical properties. In contrast to the brittle crystalline retinoic acid the complexes with polyelectrolytes are highly deformable viscoelastic materials. All materials show lamellar mesophase structures; their T g value strongly depends on the polyelectrolyte. It is suggested that these materials have great potential as pharmaceutical agents as well as models for the investigation and the mimicking of chromophores in visual pigments and photosynthetic bacteria. The properties of the complexes are examined by X-ray diffraction, differential scanning calorimetry, polarization optical microscopy, UV−vis spectroscopy, and stress−strain measurements.

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Structure-activity relationship studies of retinoid cancer inhibition

Cited by 18 publications

References 27 publications

Immobilization of Retinoic Acid by Polyamino Acids: Lamellar-Structured Nanoparticles

Immobilization of Retinoic Acid by Polyamino Acids: Lamellar-Structured Nanoparticles

Quantitative structure-activity relationship studies of RAR α, β, γ retinoid agonists

Immobilization of Retinoic Acid by Cationic Polyelectrolytes

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