at Google ScholarTitle data
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.
Vol. 13
(2022)
Issue 11
.
- pp. 1783-1790.
ISSN 1948-5875
DOI: https://doi.org/10.1021/acsmedchemlett.2c00403
Abstract in another language
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 Especially, the alkyne 3f, originally made for intracellular localization studies using click chemistry, showed an overall high activity in all assays performed.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.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Keywords: | Naphthopyran; Multitargeting; c-Myb; Microtubule; Antiangiogenesis |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Professor Developmental Biology > Professor Developmental Biology - Univ.-Prof. Dr. Gerrit Begemann Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Organic Chemistry I - Univ.-Prof. Dr. Rainer Schobert |
| Result of work at the UBT: | Yes |
| DDC Subjects: | 500 Science > 540 Chemistry |
| Date Deposited: | 28 Nov 2023 12:54 |
| Last Modified: | 28 Nov 2023 12:54 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/87894 |