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Köhler, Leonhard ; Reich, Sebastian ; Yusenko, Maria ; Klempnauer, Karl-Heinz ; Shaikh, Amin H. ; Ahmed, Khursheed ; Begemann, Gerrit ; Schobert, Rainer ; Biersack, Bernhard:
A New Naphthopyran Derivative Combines c-Myb Inhibition, Microtubule-Targeting Effects, and Antiangiogenic Properties.
In: ACS Medicinal Chemistry Letters.
Bd. 13
(2022)
Heft 11
.
- S. 1783-1790.
ISSN 1948-5875
DOI: https://doi.org/10.1021/acsmedchemlett.2c00403
Abstract
Based on the promising c-Myb inhibitor 1b, a series of 2-amino-4-aryl-4H-naphtho[1,2-b]pyran-3-carbonitriles (1a, 2a–q, 3a–g) were repurposed or newly synthesized via a three-component reaction of 1-naphthol, and various aryl aldehydes and malononitrile and screened for their c-Myb inhibitory activities. 1b also served as a lead compound for seven new naphthopyran derivatives (3a–f), which were cytotoxic with nanomolar IC50 values, to inhibit the polymerization of tubulin, and to destabilize microtubules in living cells. Especially, the alkyne 3f, originally made for intracellular localization studies using click chemistry, showed an overall high activity in all assays performed. A strong G2/M cell cycle arrest was detected, which resulted in a distinct increase in sub-G1 cells through the induction of effector caspases 3 and 7. Inhibition of angiogenesis was confirmed in vitro and in vivo. In summary, 3f was found to be a pleiotropic compound with high selectivity for cancer cells, combining c-Myb inhibitory, microtubule destabilizing, and antiangiogenic effects.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Keywords: | Naphthopyran; Multitargeting; c-Myb; Microtubule; Antiangiogenesis |
| Institutionen der Universität: | Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Biologie > Professur Entwicklungsbiologie > Professur Entwicklungsbiologie - Univ.-Prof. Dr. Gerrit Begemann Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige ProfessorInnen > Lehrstuhl Organische Chemie I - Univ.-Prof. Dr. Rainer Schobert |
| Titel an der UBT entstanden: | Ja |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
| Eingestellt am: | 28 Nov 2023 12:54 |
| Letzte Änderung: | 28 Nov 2023 12:54 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/87894 |