Naslov
Itaconic acid hybrids as potential anticancer agents

Autori
Perković, Ivana ; Beus, Maja ; Schols, Dominique ; Persoons, Leentje ; Zorc, Branka

Izvornik
Molecular diversity (1381-1991) 26 (2022); 1-14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Itaconic acid ; Hybrid ; Michael acceptor ; Anticancer activity ; Antiviral activity

Sažetak
In this paper, we report the synthesis of novel hybrids 2–14 based on itaconic acid and fluoroaniline, pyridine, indole and quinoline scaffolds. Itaconic acid is a naturally occurring compound with a Michael acceptor moiety, a key structural feature in several anticancer and antiviral drugs, responsible for the covalent binding of a drug to the cysteine residue of a specific protein. Aromatic parts of the hybrids also come from the substances reported as anticancer or antiviral agents. The synthetic route employed to access the amido- ester hybrids 2–13 used monomethyl itaconate or monomethyl itaconyl chloride and corresponding amines as the starting materials. Dimers 14 and 15 with two aminoindole or mefloquine moieties were prepared from itaconic acid and corresponding amino derivative, using standard coupling conditions (HATU/DIEA). All hybrids exerted anticancer effects in vitro against almost all the tumour cell lines that were evaluated (MCF-7, HCT 116, H460, LN-229, Capan- 1, DND-41, HL-60, K-562, Z- 138). Solid tumour cells were, in general, more responsive than the haematological cancer cells. The MCF-7 breast adenocarcinoma cell line appeared the most sensitive. Amido-ester 12 with chloroquine core and mefloquine homodimer 15 showed the highest activity with GI50 values between 0.7 and 8.6 µM. In addition, compound 15 also exerted antiviral activity against Zika virus and Coxsackievirus B4 in low micromolar concentrations.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA