Naslov
Itaconic acid-aminoquinoline hybrids as potential anticancer agents

Autori
Perković, Ivana ; Beus, Maja ; Pavić, Kristina ; Zorc, Branka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Knjiga sažetaka, 6. hrvatski kongres farmacije, Dubrovnik, 4. do. 7. 4. 2019. / Zorc, Branka - Zagreb : Hrvatsko farmaceutsko društvo, 2019, 175-175

ISBN
978-953-7897-11-6

Skup
6. Hrvatski kongres farmacije s međunarodnim sudjelovanjem: Novo doba farmacije: Spremni za izazove

Mjesto i datum
Dubrovnik, Hrvatska, 04.04.2019. - 07.04.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
primaquine, itaconic acid

Sažetak
Itaconic acid (methylenesuccinic acid) and related compounds with itaconate core are naturally occurring substances isolated from various species of lichen and fungi. Itaconic acid is a dicarboxylic acid with exometylene moiety conjugated with carbonyl group. Such compounds are considered the best substrates in the conjugate addition (Michael addition). Michael acceptors are present in several anticancer drugs (afatinib, ibrutinib, osimertinib, neratinib), which irreversibly bind to the cysteine residue of a specific protein (1). Another Michael acceptor drug, a loop diuretic ethacrynic acid, inhibits isoenzymes of glutathione S-transferase overexpressed in tumor tissues and reduces chemotherapy drug resistance (2). Itaconic acid is a macrophage-specific metabolite which mediates crosstalk between macrophage metabolism and peritoneal tumors (3), whereas chaetomellic acids, itaconic acid derivatives from lichen Chaetomella, are known as strong farnesyltransferase inhibitors and valuable leads for the development of anticancer drugs (4). Having all this in mind, we have prepared a series of novel itaconic acid-aminoquinoline hybrids as potential anticancer agents. Two 8-aminoquinoline and three 4-aminoquinoline amides were synthesized starting from commercially available itaconic acid monomethyl ester and primaquine (PQ), N1-(7-chloroquinolin-4-yl)butane-1, 4-diamine and N1-(2, 8-bis(trifluoromethyl)quinolin-4-yl)butane-1, 4-diamine, respectively. 1-[Bis(dimethylamino)methylene]-1H-1, 2, 3-triazolo[4, 5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was used as the coupling reagent, together with N, N-diisopropylethylamine (DIEA). Three itaconic acid diamides with PQ, N1-(7-chloroquinolin-4-yl)butane-1, 4-diamine or N1-(2, 8-bis(trifluoromethyl)quinolin-4-yl)butane-1, 4-diamine were prepared from itaconic acid and corresponding aminoquinoline in molar ratio 1:2, employing HATU/DIEA coupling method. Evaluation of antiproliferative activity of the title compounds against a number of cancer cell lines is in progress. 1. P. A. Jackson et al., J. Med. Chem. 60 (2017) 839. 2. J. C. Somberg et al., Am. J. Ther. 16 (2009) 102. 3. J. M. Weiss et al., J. Clin. Invest. 128 (2018) 3794. 4. http://www.abcam.com/chaetomellic-acid-a-ab141622.html

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA