Abstract
Methenolone and drostanolone are two popular synthetic anabolic-androgenic agents and dihydrotestosterone derivatives which belong to the steroid family. Two esterified prodrugs of methenolone and drostanolone, in the form of methenolone and drostanolone enanthate, have been described from a structural point of view. The crystal structure of drostanolone enanthate was determined by single crystal X-ray diffraction, while the crystal structure of methenolone enanthate was solved by the powder X-ray diffraction technique. The nature and magnitudes of intermolecular interactions were analysed quantitatively by means of crystal lattice energies and Hirshfeld surfaces.
Acknowledgements
This work was supported by a grant from the Romanian Ministry of Research, Innovation and Digitization, under Core Program, project number 19 35 02 02 and UEFISCDI projects PN-III-P1-1.1-PD-2019-0701. The service for the Oxford SuperNova diffractometer was supported by the Ministry of Research, Innovation, and Digitization through Programme 1-Development of the National Research and Development System, Subprogramme 1.2-Institutional Performance-Funding Projects for Excellence in RDI, Contract No. 37PFE/30.12.2021.
-
Research ethics: Not applicable.
-
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
-
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission
-
Competing interests: The authors states no conflict of interest
-
Research funding: Financial support from the Ministry of Research and Innovation – MCI, Core Programme, 19 35 02 02 and UEFISCDI projects PN-III-P1-1.1-PD-2019-0701.
-
Data availability: The raw data can be obtained on request from the corresponding author.
References
1. Lednicer, D Steroid Chemistry at a Glance, 1st ed.; Wiley: Chichester, UK, 2010.10.1002/9780470973639Search in Google Scholar
2. Mooradian, A. D., Morley, J. E., Korenman, S. G. Biological actions of androgens. Endocr. Rev. 1987, 8, 1–28; https://doi.org/10.1210/edrv-8-1-1.Search in Google Scholar PubMed
3. Shahidi, N. T. A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin. Ther. 2001, 23, 1355–1390; https://doi.org/10.1016/s0149-2918(01)80114-4.Search in Google Scholar PubMed
4. Kicman, A. T. Pharmacology of anabolic steroids. Br. J. Pharmacol. 2008, 154, 502–521; https://doi.org/10.1038/bjp.2008.165.Search in Google Scholar PubMed PubMed Central
5. Vermeulen, A. Longacting steroid preparations. Acta Clin. Belg. 1975, 30, 48–55; https://doi.org/10.1080/17843286.1975.11716973.Search in Google Scholar PubMed
6. Lockner, L. Treatment of refractory anemias with methenolone. Acta Med. Scand. 1979, 205, 97–101; https://doi.org/10.1111/j.0954-6820.1979.tb06010.x.Search in Google Scholar PubMed
7. Chowdhury, M. S., Banks, A. J., Bond, W. H., Jones, W. G., Ward, H. W. A comparison of drostanolone propionate (Masteril) and nandrolone decanoate (Deca-durabolin) in the treatment of breast carcinoma. Clin. Oncol. 1976, 2, 203–206.Search in Google Scholar
8. Llewellyn, W. Anabolics, 11th ed.; Molecular Nutrition Llc: Jupiter, Florida, 2017; pp. 324–326.Search in Google Scholar
9. Braunstein, G. D. The influence of anabolic steroids on muscular strength. Princ. Med. Biol. 1997, 8, 465–474.10.1016/S1569-2582(97)80048-7Search in Google Scholar
10. Borodi, G., Turza, A., Bende, A. Exploring the polymorphism of drostanolone propionate. Molecules 2020, 25, 1436; https://doi.org/10.3390/molecules25061436.Search in Google Scholar PubMed PubMed Central
11. Turza, A., Borodi, G., Muresan-Pop, M., Ulici, A. Polymorphism and β-cyclodextrin complexation of methyldrostanolone. J. Mol. Struct. 2022, 1250, 131852; https://doi.org/10.1016/j.molstruc.2021.131852.Search in Google Scholar
12. Turza, A., Borodi, G., Pop, A., David, M. Structural studies of some androstane based prodrugs. J. Mol. Struct. 2022, 1248, 131440; https://doi.org/10.1016/j.molstruc.2021.131440.Search in Google Scholar
13. CrysAlis Pro 1.171.38.46; Rigaku Oxford Diffraction: Yarnton, Oxfordshire, England, 2015.Search in Google Scholar
14. Sheldrick, G. M. A short history of Shelx. Acta Crystallogr. A: Found. Adv. 2008, 64, 112–122; https://doi.org/10.1107/s0108767307043930.Search in Google Scholar PubMed
15. Sheldrick, G. M. Crystal structure refinement with Shelxl. Acta Crystallogr., Sect. C: Struct. Chem. 2015, 71, 3–8; https://doi.org/10.1107/s2053229614024218.Search in Google Scholar
16. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K., Puschmann, H. A complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 2009, 42, 339–341; https://doi.org/10.1107/s0021889808042726.Search in Google Scholar
17. Gavezzotti, A. Efficient computer modeling of organic materials. The atom–atom, Coulomb–London–Pauli (AA-CLP) model for intermolecular electrostatic-polarization, dispersion and repulsion energies. New J. Chem. 2011, 35, 1360–1368; https://doi.org/10.1039/c0nj00982b.Search in Google Scholar
18. Spackman, M. A., McKinnon, J. J. Fingerprinting intermolecular interactions in molecular crystals. CrystEngComm 2002, 4, 378–392; https://doi.org/10.1039/b203191b.Search in Google Scholar
19. Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D., Spackman, M. A. CrystalExplorer17; University of Western Australia: Perth, 2017.Search in Google Scholar
20. Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D., Spackman, M. A. CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. J. Appl. Crystallogr. 2021, 54, 1006–1011; https://doi.org/10.1107/s1600576721002910.Search in Google Scholar PubMed PubMed Central
21. Mackenzie, C. F., Spackman, P. R., Jayatilaka, D., Spackman, M. A. CrystalExplorer model energies and energy frameworks: extension to metal coordination compounds, organic salts, solvates and open-shell systems. IUCrJ 2017, 4, 575–587; https://doi.org/10.1107/s205225251700848x.Search in Google Scholar
22. Neumann, M. A. Crystal X-cell: a novel indexing algorithm for routine tasks and difficult cases. J. Appl. Crystallogr. 2003, 36, 356–365; https://doi.org/10.1107/s0021889802023348.Search in Google Scholar
23. MATERIALS STUDIO (v8.0.0.843); Dassault Systèmes BIOVIA: San Diego, 2014.Search in Google Scholar
24. Favre-Nicolin, V., Cerny, R. FOX free objects for crystallography’: a modular approach to ab initio structure determination from powder diffraction. Biol. Mass Spectrom. 2002, 35, 734–743; https://doi.org/10.1107/s0021889802015236.Search in Google Scholar
25. Meden, A. Crystal structure solution from powder diffraction data – state of the art and perspectives. Croat. Chem. Acta 1998, 71, 615–633.Search in Google Scholar
26. Caglioti, G., Paoletti, A., Ricci, F. P. Choice of collimators for a crystal spectrometer for neutron diffraction. Nucl. Instrum. 1958, 3, 223–228; https://doi.org/10.1016/0369-643x(58)90029-x.Search in Google Scholar
27. Weeks, C. M., Duax, W. L., Osawa, Y. 2α-Hydroxytestosterone diacetate. Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. 1975, 31, 1502–1504; https://doi.org/10.1107/s0567740875005559.Search in Google Scholar
28. Isaacs, N. W., Motherwell, W. D. S., Coppola, J. C., Kennard, O. Crystal and molecular structure of 17α-hydroxyandrost-4-en-3one (epitestosterone). J. Chem. Soc., Perkin Trans. 2 1972, 2335–2339; https://doi.org/10.1039/p29720002335.Search in Google Scholar
29. Duax, W. L., Eger, C., Pokrywiecki, S., Osawa, Y. Crystalline molecular structures of two derivatives of 2β-hydroxytestosterone having unusual a-ring conformation. J. Med. Chem. 1971, 14, 295–300; https://doi.org/10.1021/jm00286a007.Search in Google Scholar PubMed
30. Karpinska, J., Erxleben, A., McArdle, P. 17β-Hydroxy-17α-methylandrostano[3,2-c]pyrazole, stanozolol: the crystal structures of polymorphs 1 and 2 and 10 solvates. Cryst. Growth Des. 2011, 11, 2829–2838; https://doi.org/10.1021/cg101651p.Search in Google Scholar
31. Rajnikant, Dinesh, Mousmi Analysis of C–H⋯O hydrogen interactions and TLS parameters in 5a-Oxa-β-homo-5α-cholestan-6-one. J. Chem. Crystallogr. 2006, 36, 343–348; https://doi.org/10.1007/s10870-006-9070-z.Search in Google Scholar
32. Courseille, C., Precigoux, C., Leroy, F., Busetta, B. 5α-Androstan-17β-Ol-3-one, C19H30O2. Cryst. Struct. Commun. 1973, 2, 441.10.1107/S0567740874008004Search in Google Scholar
33. Busetta, B., Courseille, C., Fornies-Marquina, J. M., Hospital, M 5α-Androstan-17β-Ol-3-one, C19H30O2. Cryst. Struct. Commun. 1972, 1, 43.Search in Google Scholar
34. Takata, N., Shiraki, K., Takano, R., Hayashi, Y., Terada, K. Cocrystal screening of stanolone and mestanolone using slurry crystallization. Cryst. Growth Des. 2008, 8, 3032–3037; https://doi.org/10.1021/cg800156k.Search in Google Scholar
35. Gaedecki, Z., Grochulski, P., Wawrzak, Z. Structure of 17-α-methyl-testosterone semihydrate C20H30O2·1/2H2O. J. Crystallogr. Spectrosc. Res. 1989, 19, 577–587; https://doi.org/10.1007/bf01185393.Search in Google Scholar
36. Rendle, D. F., Trotter, J. Crystal and molecular structure of 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one. J. Chem. Soc., Perkin Trans. 2 1975, 1361–1365; https://doi.org/10.1039/p29750001361.Search in Google Scholar
37. Babenek, E., Kadela-Tomanek, M., Chrobak, E., Jastrzebska, M., Ksiazek, M. Synthesis and structural characterization of a new 1,2,3-triazole derivative of pentacyclic triterpene. Crystals 2022, 12, 422; https://doi.org/10.3390/cryst12030422.Search in Google Scholar
38. Zeng, H., Xiong, J., Zhao, Z., Qiao, J., Xu, D., Miao, M., He, L., Wu, X. Preparation of progesterone Co-crystals based on crystal engineering strategies. Molecules 2019, 24, 3936; https://doi.org/10.3390/molecules24213936.Search in Google Scholar PubMed PubMed Central
39. Borodi, G., Turza, A., Camarasan, P. A., Ulici, A. Structural studies of trenbolone, trenbolone acetate, hexahydrobenzylcarbonate and enanthate esters. J. Mol. Struct. 2020, 1212, 128127; https://doi.org/10.1016/j.molstruc.2020.128127.Search in Google Scholar
40. Turza, A., Miclaus, M. O., Pop, A., Borodi, G. Crystal and molecular structures of boldenone and four boldenone steroid esters. Z. Kristallogr. 2019, 234, 671–683; https://doi.org/10.1515/zkri-2019-0030.Search in Google Scholar
41. Turza, A., Pascuta, P., Mare, L., Borodi, G., Popescu, V. Structural insights and intermolecular energy for some medium and long-chain testosterone esters. Molecules 2023, 28, 3097; https://doi.org/10.3390/molecules28073097.Search in Google Scholar PubMed PubMed Central
42. Turza, A., Popescu, V., Mare, L., Borodi, G. Structural aspects and intermolecular energy for some short testosterone esters. Materials 2022, 15, 7245; https://doi.org/10.3390/ma15207245.Search in Google Scholar PubMed PubMed Central
43. Mare, L., Muresan-Pop, M., Purcea Lopes, P. M., Turza, A., Borodi, G., Popescu, V. Crystal structure and intermolecular energy for some nandrolone esters. Molecules 2023, 28, 7179; https://doi.org/10.3390/molecules28207179.Search in Google Scholar PubMed PubMed Central
Supplementary Material
The article contains supplementary material (https://doi.org/10.1515/zkri-2023-0050).
© 2024 Walter de Gruyter GmbH, Berlin/Boston
