Boulton-Katritzky Rearrangement of 5-Substituted Phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles as a Synthetic Path to Spiropyrazoline Benzoates and Chloride with Antitubercular Properties
| Autor: | L. Chingissova, Lyudmila A. Kayukova, Gulnur Dyusembaeva, Venera Bismilda, K. Akatan, Kaldybai Praliyev, Gulnur Baitursynova, Anna V. Vologzhanina, Asem B. Uzakova |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
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2 4-oxadiazoles Antitubercular Agents Pharmaceutical Science Microbial Sensitivity Tests 010402 general chemistry Benzoates 01 natural sciences Medicinal chemistry Chloride Article Analytical Chemistry lcsh:QD241-441 Structure-Activity Relationship in vitro antitubercular screening Chlorides lcsh:Organic chemistry Spectroscopy Fourier Transform Infrared Drug Discovery medicine Humans Tuberculosis Physical and Theoretical Chemistry Oxadiazoles Molecular Structure 010405 organic chemistry Chemistry spiropyrazolinium compounds Organic Chemistry Intermolecular force Stereoisomerism Biological activity Mycobacterium tuberculosis Nuclear magnetic resonance spectroscopy molecular docking In vitro 0104 chemical sciences X-ray diffraction Molecular Docking Simulation Chemistry (miscellaneous) X-ray crystallography Molecular Medicine Acid–base reaction medicine.drug |
| Zdroj: | Molecules Volume 26 Issue 4 Molecules, Vol 26, Iss 967, p 967 (2021) |
| ISSN: | 1420-3049 |
| Popis: | The analysis of stability of biologically active compounds requires an accurate determination of their structure. We have found that 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles are generally unstable in the presence of acids and bases and are rearranged into the salts of spiropyrazolinium compounds. Hence, there is a significant probability that it is the rearranged products that should be attributed to biological activity and not the primarily screened 5-aryl-3-(2-aminoethyl)-1,2,4-oxadiazoles. A series of the 2-amino-8-oxa-1,5-diazaspiro[4.5]dec-1-en-5-ium (spiropyrazoline) benzoates and chloride was synthesized by Boulton–Katritzky rearrangement of 5-substituted phenyl-3-[2-(morpholin-1-yl)ethyl]-1,2,4-oxadiazoles and characterized using FT-IR and NMR spectroscopy and X-ray diffraction. Spiropyrazolylammonium chloride demonstrates in vitro antitubercular activity on DS (drug-sensitive) and MDR (multidrug-resistant) of MTB (M. tuberculosis) strains (1 and 2 µg/mL, accordingly) equal to the activity of the basic antitubercular drug rifampicin spiropyrazoline benzoates exhibit an average antitubercular activity of 10–100 μg/mL on MTB strains. Molecular docking studies revealed a series of M. tuberculosis receptors with the energies of ligand–receptor complexes (−35.8–−42.8 kcal/mol) close to the value of intermolecular pairwise interactions of the same cation in the crystal of spiropyrazolylammonium chloride (−35.3 kcal/mol). However, only in complex with transcriptional repressor EthR2, both stereoisomers of the cation realize similar intermolecular interactions. |
| Databáze: | OpenAIRE |
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