Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II

Hamed A, Abdelwahab AB, Soltan MM, Stammler H-G, Shaaban M (2022)
Journal of Molecular Structure 1258: 132655.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Hamed, Abdelaaty; Abdelwahab, Ahmed B.; Soltan, Maha M.; Stammler, Hans-GeorgUniBi; Shaaban, Mohamed
Abstract / Bemerkung
Butyrolactone I is a natural butenolide that has been isolated from the culture broth of the thermophilic fungus Aspergillus terreus TM8. Its structure was determined by HR-ESI-MS as well as NMR spectroscopic data. The crystal structure and absolute configuration of butyrolactone I are reported herein for the first time based on single crystal X-ray diffraction. Butyrolactone I is known as a highly selective inhibitor of cyclin-dependent protein kinases which inhibits cell cycle progression at the G(1)/S and G(2)/M transitions. Through this study, we investigate the action of butyrolactone I against the human topoisomerase II (topo II) and vascular endothelial growth factor receptor2 (VEGFR2) kinase. The molecular docking results introduced butyrolactone I either as a catalytic inhibitor against topo II alpha or a poison to topo II beta while the first mechanism is the most likely to take place. Contrarily to topo II, butyrolactone I displayed a low affinity toward VEGFR2 kinase. In the light of the molecular docking investigation, butyrolactone I, in synchronizing to a catalytic inhibitor and poison control, was subjected to the in vitro topo II alpha relaxation assay. The results revealed the capability of butyrolactone I to suppress the relaxation of the supercoiled DNA plasmid in a concentration-dependent manner, with IC50 value of 6.64 mu M. Interestingly, this IC50 was more comparable to the catalytic inhibitor (staurosporine) rather than the poison one (doxorubicin). (c) 2022 Elsevier B.V. All rights reserved.& nbsp;
Stichworte
Butyrolactone I; Absolute configuration; X-ray analysis; Molecular; docking; Topoisomerase II alpha inhibitor
Erscheinungsjahr
2022
Zeitschriftentitel
Journal of Molecular Structure
Band
1258
Art.-Nr.
132655
ISSN
0022-2860
eISSN
1872-8014
Page URI
https://pub.uni-bielefeld.de/record/2963824

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Hamed A, Abdelwahab AB, Soltan MM, Stammler H-G, Shaaban M. Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II. Journal of Molecular Structure . 2022;1258: 132655.
Hamed, A., Abdelwahab, A. B., Soltan, M. M., Stammler, H. - G., & Shaaban, M. (2022). Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II. Journal of Molecular Structure , 1258, 132655. https://doi.org/10.1016/j.molstruc.2022.132655
Hamed, A., Abdelwahab, A. B., Soltan, M. M., Stammler, H. - G., and Shaaban, M. (2022). Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II. Journal of Molecular Structure 1258:132655.
Hamed, A., et al., 2022. Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II. Journal of Molecular Structure , 1258: 132655.
A. Hamed, et al., “Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II”, Journal of Molecular Structure , vol. 1258, 2022, : 132655.
Hamed, A., Abdelwahab, A.B., Soltan, M.M., Stammler, H.-G., Shaaban, M.: Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II. Journal of Molecular Structure . 1258, : 132655 (2022).
Hamed, Abdelaaty, Abdelwahab, Ahmed B., Soltan, Maha M., Stammler, Hans-Georg, and Shaaban, Mohamed. “Isolation, crystal structure, absolute configuration and molecular docking of butyrolactone I as a potential inhibitor of topoisomerase II”. Journal of Molecular Structure 1258 (2022): 132655.

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