Design, synthesis and antitumor activity study of a gemcitabine prodrug conjugated with a HDAC6 inhibitor.
Bioorg Med Chem Lett
; 72: 128881, 2022 09 15.
Article
in En
| MEDLINE
| ID: mdl-35810950
ABSTRACT
Gemcitabine, as a first-line antitumor drug, has attracted extensive attention. However the occurrence of drug resistance limits its clinical utilization. In this paper, a gemcitabine prodrug GZ was designed and synthesized by conjugation of gemcitabine with a newly reported HDAC6 selective inhibitor pentadecanoic acid. GZ displayed high cytotoxicity to nine cancer cell lines with IC50 values in the low micromolar range. In vivo, GZ displayed superior antitumor activity to gemcitabine in a 4T1 tumor xenograft model without obvious pathological damage to important organs of mice. Our study showed that compound GZ is a potential gemcitabine prodrug, which is worthy of further antitumor activity exploration.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2022
Document type:
Article
Affiliation country:
China