Results
Title

Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation.

Authors

Salerno, Loredana; Vanella, Luca; Sorrenti, Valeria; Consoli, Valeria; Ciaffaglione, Valeria; Fallica, Antonino N.; Canale, Vittorio; Zajdel, Paweł; Pignatello, Rosario; Intagliata, Sebastiano

Abstract

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.

Subjects

FLUOROURACIL; HEME; ANTINEOPLASTIC agents; EPITHELIAL cells; PRODRUGS; ANTIBODY-dependent cell cytotoxicity; CELL survival

Publication

Journal of Enzyme Inhibition & Medicinal Chemistry, 2021, Vol 36, Issue 1, p1377

ISSN

1475-6366

Publication type

Academic Journal

DOI

10.1080/14756366.2021.1928111