Topical Corticosteroids, Structure-Activity and the Glucocorticoid Receptor: Discovery and Development—A Process of ‘‘Planned Serendipity’’

Katz, M; Gans, Eugene H.

doi:10.1002/jps.21222

Cited by 43 publications

(33 citation statements)

References 35 publications

(44 reference statements)

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“…Fra is the most hydrophilic compound and showed less affinity for the E and D. For example, the three formulations of Fra show higher amounts of the substance in the RF than in the upper layer, the D. This is clearly more marked for Fra‐cre. This special behaviour is consistent in the three formulations and can be explained by the presence of the acetonide group in the D ring, which enhances the penetrability and the percutaneous absorption of this type of corticoid . In summary, in Clo, Bet and Fra, the retention in the tissue (E + D) is always greater when PG is employed.…”

Section: Resultssupporting

confidence: 60%

In vitro penetration through the skin layers of topically applied glucocorticoids

Carrer

Alonso

Oliver

et al. 2018

Drug Testing and Analysis

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Corticoids are actives widely used in the treatment of skin diseases. This work aims to study the penetration of 3 corticoids (betamethasone, clobetasol, and flurandrenolide), their relationship with their Log D values and the effects of the vehicles. The 3 compounds were applied on a Franz-type diffusion cell in propylene glycol solution and their respective commercial creams and ointments. The active amounts found in the stratum corneum, epidermal, and dermal layers of the skin were investigated. Their diffusions were greatly affected by the formulation; moreover higher amounts of substance in the epidermis and dermis were detected in ointments than in creams. The enhancement effect of propylene glycol was also observed. The differences between the 3 substances could be related to their lipophilicity, molecular structure, and molecular weight. The more hydrophobic compounds (clobetasol and betamethasone) are present in higher amounts in the epidermis and dermis, while the hydrophilic compound (flurandrenolide) is mostly present in the receptor fluid.

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Section: Resultssupporting

confidence: 60%

In vitro penetration through the skin layers of topically applied glucocorticoids

Carrer

Alonso

Oliver

et al. 2018

Drug Testing and Analysis

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“…The acetonide component markedly enhances the penetration properties of triamcinolone, making it more active topically. 16 These properties may have caused triamcinolone acetonide to be more effective than betamethasone. Although the betamethasone doses used previously were within the safe clinical range, a lower, less potent dose of triamcinolone has an advantage over betamethasone given the potential adverse effects associated with steroid use, including infections such as candidiasis, numbness, and dry mouth and throat.…”

Section: Discussionmentioning

confidence: 99%

Application of triamcinolone acetonide paste to the endotracheal tube reduces postoperative sore throat: a randomized controlled trial

Park

Kim

Lee

et al. 2011

Can J Anesth/J Can Anesth

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“…, '-Dihydroxy ketone motifs are useful synthetic intermediates for the synthesis of a range of compounds such as ketosugars, and are also present in other natural products including the pharmacologically important corticosteroids [2][3][4]. There are several synthetic routes that have been described, however a biocatalytic approach using the enzyme TK is a concise method for generating 1,3-dihydroxy ketones.…”

Section: '-Dihydroxy Ketones and 2-amino-13-diols: Biocatalytic Stmentioning

confidence: 98%

α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts

Hailes¹,

Dalby²,

Lye³

et al. 2010

COC

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There is increasing interest in the use of biocatalysts in synthetic applications due to their ability to achieve highly stereoselective and atom efficient conversions. Recent developments in molecular biology techniques and synthetic biology have also enhanced potential applications using non-natural substrates. Here we review strategies to , '-dihydroxy ketones and 2-amino-1,3-diols via the use of transketolase, a carbon-carbon bond forming biocatalyst, and the enzyme transaminase which converts aldehydes and ketones to amines. Using an integrated strategy we have investigated new chemistries and assays, identified novel biocatalysts and used directed evolution strategies, together with miniaturization studies and modelling to achieve rapid and predictive process scale-up.The use of biocatalysts for the synthesis of biologically active compounds is of increasing interest to the chemical, pharmaceutical and biotechnology sectors in the search for sustainable, cost effective, synthetic strategies. In addition, developments in molecular biology tools and protein and pathway engineering, leading to improved biocatalyst substrate tolerance, specific activities and processing properties are resulting in extensive possibilities for the use of enzymes in synthesis. Current interest in synthetic biology approaches and also cascade reactions, with applications in biofuel synthesis as well as routes to pharmaceuticals, will result in exciting developments and opportunities using biocatalysts in the next decade. At UCL, a multidisciplinary approach has been established in the Departments of Chemistry, Biochemical Engineering and Structural and Molecular Biology (BiCE programme) focusing initially on biocatalytic approaches to , '-dihydroxy ketones and 2-amino-1,3-diols [1]. This has led to the development of new biocatalysts and chemistries and new miniaturization tools for rapid and predictable process scale-up. This review will focus on the use of two enzymes, transketolase (TK) (EC 2.2.1.1) and transaminase (TAm) for the synthesis of the important structural motifs , '-dihydroxy ketones and 2-amino-1,3-diols and biocatalyst scale-up tools.

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Topical Corticosteroids, Structure-Activity and the Glucocorticoid Receptor: Discovery and Development—A Process of ‘‘Planned Serendipity’’

Cited by 43 publications

References 35 publications

In vitro penetration through the skin layers of topically applied glucocorticoids

In vitro penetration through the skin layers of topically applied glucocorticoids

Application of triamcinolone acetonide paste to the endotracheal tube reduces postoperative sore throat: a randomized controlled trial

α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts

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Topical Corticosteroids, Structure-Activity and the Glucocorticoid Receptor: Discovery and Development—A Process of ‘‘Planned Serendipity’’

Cited by 43 publications

References 35 publications

In vitro penetration through the skin layers of topically applied glucocorticoids

In vitro penetration through the skin layers of topically applied glucocorticoids

Application of triamcinolone acetonide paste to the endotracheal tube reduces postoperative sore throat: a randomized controlled trial

&#945;, &#945; -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts

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α, α -Dihydroxy Ketones and 2-Amino-1,3-diols: Synthetic and Process Strategies Using Biocatalysts