Crystal engineering of exemestane to obtain a co-crystal with enhanced urease inhibition activity
| Autor: | Syeda Saima Fatima, Rajesh Kumar, M. Iqbal Choudhary, Sammer Yousuf |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | IUCrJ, Vol 7, Iss 1, Pp 105-112 (2020) |
| Druh dokumentu: | article |
| ISSN: | 2052-2525 20522525 |
| DOI: | 10.1107/S2052252519016142 |
| Popis: | Co-crystallization is a phenomenon widely employed to enhance the physio-chemical and biological properties of active pharmaceutical ingredients (APIs). Exemestane, or 6-methylideneandrosta-1,4-diene-3,17-dione, is an anabolic steroid used as an irreversible steroidal aromatase inhibitor, which is in clinical use to treat breast cancer. The present study deals with the synthesis of co-crystals of exemestane with thiourea by liquid-assisted grinding. The purity and homogeneity of the exemestane–thiourea (1:1) co-crystal were confirmed by single-crystal X-ray diffraction followed by thermal stability analysis on the basis of differential scanning calorimetry and thermogravimetric analysis. Detailed geometric analysis of the co-crystal demonstrated that a 1:1 co-crystal stoichiometry is sustained by N—H...O hydrogen bonding between the amine (NH2) groups of thiourea and the carbonyl group of exemestane. The synthesized co-crystal exhibited potent urease inhibition activity in vitro (IC50 = 3.86 ± 0.31 µg ml−1) compared with the API (exemestane), which was found to be inactive, and the co-former (thiourea) (IC50 = 21.0 ± 1.25 µg ml−1), which is also an established tested standard for urease inhibition assays in vitro. The promising results of the present study highlight the significance of co-crystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients. Furthermore, the role of various hydrogen bonds in the crystal stability is successfully analysed quantitatively using Hirshfeld surface analysis. |
| Databáze: | Directory of Open Access Journals |
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