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Сравнительная характеристика фармацевтических субстанций активаторов сигнального пути STING
Introduction. Benzothiophene-oxobutanoic acid (MSA-2) and its novel derivative SAD-2 are low-molecular-weight non-nucleotide activators of the STING protein, which is an essential component of the cGAS-STING signaling pathway and a promising target for anti-tumor biotherapy. The pharmaceutical development of their dosage forms begins with the study of the physical and chemical properties of the substances to justify the introduction of excipients. Purpose of the study. Comparative characteristics of pharmaceutical substances of STING signaling pathway activators − MSA-2 and SAD-2. Material and methods. The objects of the study were the substances MSA-2 and SAD-2 synthesized at the N.N. Blokhin NMRCO. Methods – visual (description of appearance, solubility), flask shaking (lipophilicity), spectrophotometric. Results. MSA-2 is an amorphous light brown powder with a characteristic odor, SAD-2 is a fine crystalline powder with needle-shaped particles of light brown color, odorless. The powders are practically insoluble in water, moderately soluble in dimethyl sulfoxide and slightly soluble in 95% ethyl alcohol. However, MSA-2, as a weak acid, is capable of forming solutions in an alkaline medium and a phosphate-salt buffer (pH 7.4). At the same time, due to the presence of an isopropyl residue in the structure, SAD-2 is more soluble in volatile organic solvents. In the electronic absorption spectra of alcoholic dilutions of substances, 4 maxima inherent in the ultraviolet region of the spectrum were found. When assessing lipophilicity, it was found that MSA-2 and SAD-2 differ significantly in the distribution between lipophilic and aqueous media: the value of the lipophilicity index (logP) for MSA-2 is 0.7, indicating the amphiphilic properties of the compound, and SAD-2 is 2.42. Conclusion. The comparative characteristics of pharmaceutical substances MSA-2 and SAD-2 have been carried out. It has been established that the structural modification of benzothiophene-oxobutanoic acid contributes to the production of a more lipophilic derivative.