Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity
Acta Pharmaceutica Sinica B
;
(6): 1294-1308, 2020.
Article
in English
| WPRIM
| ID: wpr-828807
ABSTRACT
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent and antitumor potency. Particularly, compound was orally active and possessed excellent antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, .) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
English
Journal:
Acta Pharmaceutica Sinica B
Year:
2020
Type:
Article
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