Journal
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume 36, Issue 1, Pages 1378-1386Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2021.1928111
Keywords
Mutual prodrugs; hybrid compounds; anticancer agents; 5-fluorouracil; heme oxygenase 1; HO-1 inhibitors
Funding
- PON R&I funds 2014-2020 [CUP: E66C18001320007, AIM1872330]
- Ministry of Health [02769.N.VLY]
- Programma Ricerca di Ateneo UNICT 2020-22 linea 2
- Piano per la Ricerca 2016-2018 [57722172107]
Ask authors/readers for more resources
The first mutual prodrug of 5-fluorouracil and heme oxygenase1 inhibitor (5-FU/HO-1 hybrid) was designed, synthesised, and evaluated for its stability and cytotoxicity against cancer cell lines. The newly synthesised hybrid demonstrated drug-like properties with low toxic liabilities and potential as a novel anticancer agent, particularly effective against lung cancer cells while showing lower cytotoxicity towards healthy lung epithelial cells.
In this work, the first mutual prodrug of 5-fluorouracil and heme oxygenase1 inhibitor (5-FU/HO-1 hybrid) has been designed, synthesised, and evaluated for its in vitro chemical and enzymatic hydrolysis stability. Predicted in silico physicochemical properties of the newly synthesised hybrid (3) demonstrated a drug-like profile with suitable Absorption, Distribution, Metabolism, and Excretion (ADME) properties and low toxic liabilities. Preliminary cytotoxicity evaluation towards human prostate (DU145) and lung (A549) cancer cell lines demonstrated that 3 exerted a similar effect on cell viability to that produced by the reference drug 5-FU. Among the two tested cancer cell lines, the A549 cells were more susceptible for 3. Of note, hybrid 3 also had a significantly lower cytotoxic effect on healthy human lung epithelial cells (BEAS-2B) than 5-FU. Altogether our results served as an initial proof-of-concept to develop 5-FU/HO-1 mutual prodrugs as potential novel anticancer agents.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available