3092-61-3Relevant academic research and scientific papers
Hybrids between H2S-donors and betamethasone 17-valerate or triamcinolone acetonide inhibit mast cell degranulation and promote hyperpolarization of bronchial smooth muscle cells
Giordano, Flavia,Corvino, Angela,Scognamiglio, Antonia,Citi, Valentina,Gorica, Era,Fattorusso, Caterina,Persico, Marco,Caliendo, Giuseppe,Fiorino, Ferdinando,Magli, Elisa,Perissutti, Elisa,Santagada, Vincenzo,Severino, Beatrice,Pavese, Rocco Carmelo,Petti, Francesco,Martelli, Alma,Calderone, Vincenzo,Frecentese, Francesco
, (2021)
Glucocorticoids represent the standard gold treatment of inflammation in asthmatic patients. More recently, H2S has been described to exert positive effect on this disease. Bearing in mind that an improved pharmacological activity and a reduced toxicity can be obtained through hybridization of different molecules, simultaneously modulating multiple targets, we designed and synthesized novel betamethasone 17-valerate and triamcinolone acetonide hybrids with well-known H2S-donor moieties. Synthesized compounds have been evaluated for the potential H2S-releasing profile both in cell-free environment and into the cytosol of bronchial smooth muscle cells (BSMCs). The two hybrids 4b and 5b were investigated by molecular modelling studies and results indicated that the steric accessibility of the isothiocyanate carbon atom can account for their different H2S releasing properties. Furthermore, the most promising derivatives 4b and 5b have been tested for inhibitory effect on mast cell degranulation and for the ability to induce cell membrane hyperpolarization in BSMCs. Significant inhibitory effect on mast cell degranulation was assessed, resulting to reduce β-hexosaminidase release more efficiently than the corresponding native drugs. Both compounds determined a massive membrane hyperpolarization of BSMCs and proved to be 4-fold more effective compared to reference compound NS1619. These effects represent an enrichment of the pharmacological activity of the native drugs.
Drug-protein conjugates: Preparation of triamcinolone-acetonide containing bovine serum albumin/keyhole limpet hemocyanin-conjugates and polyclonal antibodies
Gabor,Pittner,Spiegl
, p. 775 - 780 (1995)
A radioimmunoassay has been developed for the quantitation of triamcinolone-acetonide (TAAc) at the picogram level. For use of TAAc as an antigenic epitope, first the drug was hemisuccinoylated at C-21 as confirmed by 13C-NMR- and mass spectroscopy after derivatization. This hapten was conjugated to the carrier-protein bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) by different amide-bond generating methods (imidazolide-, carbodiimide-, carbodiimide/sulfo-N-hydroxysuccinimide-, mixed anhydride-method) yielding antigens of quite different conjugation number, solubility and usefulness. The mixed anhydride-method yielded most useful soluble conjugates bearing 0.3-31.5 mol TAAc per mol carrier-protein. Coupling by the carbodiimide-method yielded insoluble conjugates, inappropriate for antigen synthesis in hapten immunoassays because of formation of coupling agent modified residues and crosslinking of the carrier-protein. Specificity of the antisera obtained by immunization with TAAc-BSA and TAAc-KLH was assessed by isolation of the soluble hapten-antibody complex and a RIA protocol was developed providing a detection limit of 200 pg (0.46 pmol) TAAc/ml sample.
STEROIDS NITROOXYDERIVATIVES
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Page/Page column 54, (2008/06/13)
The invention relates to new steroids nitrooxyderivatives, to topical pharmaceutical formulations thereof, and their use for treating skin or mucosal membrane diseases or disorders. These new steroids nitrooxyderivatives have an improved pharmacological a
