Crystal Structure and Solid-State Conformational Analysis of Active Pharmaceutical Ingredient Venetoclax
| Autor: | Zdenko Časar, Nina Žigart, Franc Perdih |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
conformation
crystal structure General Chemical Engineering Supramolecular chemistry Crystal structure law.invention Inorganic Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law crystals lcsh:QD901-999 Molecule General Materials Science Crystallization 030304 developmental biology 0303 health sciences hydrate venetoclax Hydrogen bond Venetoclax Condensed Matter Physics X-ray diffraction Crystallography chemistry 030220 oncology & carcinogenesis X-ray crystallography lcsh:Crystallography Hydrate |
| Zdroj: | Crystals, Vol 11, Iss 261, p 261 (2021) Crystals Volume 11 Issue 3 |
| ISSN: | 2073-4352 |
| Popis: | Venetoclax is an orally bioavailable, B-cell lymphoma-2 selective inhibitor used for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, and acute myeloid leukemia. Venetoclax’s crystal structure was until now determined only when it was bound to a B-cell lymphoma-2 (BCL-2) protein, while the crystal structure of this active pharmaceutical ingredient alone has not been reported yet. Herein, we present the first successful crystallization, which provided crystals of venetoclax suitable for X-ray diffraction analysis. The crystal structure of venetoclax hydrate was successfully determined. The asymmetric unit is composed of two crystallographically independent molecules of venetoclax and two molecules of interstitial water. Intramolecular N–H⋯O hydrogen bonding is present in both molecules, and a molecular overlay shows differences in their molecular conformations, which is also observed in respect to venetoclax molecules from known crystal structures of BCL-2:venetoclax complexes. A supramolecular structure is achieved through various N–H⋯N, O–H⋯O, C–H⋯O, C–H⋯π, C–Cl⋯π, ONO⋯π, and π⋯π interactions. The obtained crystals were additionally characterized with spectroscopic techniques, such as IR and Raman, as well as with thermal analysis. |
| Databáze: | OpenAIRE |
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