Naslov
Cytostatic activity of novel primaquine-vorinostat hybrid drugs

Autori
Mlinarić, Zvonimir ; Beus, Maja ; Antunović, Maja ; Marijanović, Inga ; Rajić Džolić, Zrinka ; Zorc, Branka

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

Izvornik
Knjiga sažetaka / Vrsaljko, Domagoj ; Dejanović, Igor ; Žižek, Krunoslav - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2018, 173-173

ISBN
978-953-6894-62-8

Skup
XII. susret mladih kemijskih inženjera (SMLKI 2018)

Mjesto i datum
Zagreb, Hrvatska, 22.02.2018. - 23.02.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
primaquine ; vorinostat ; hybrid drugs ; cytostatic activity

Sažetak
Some of the most important epigenetic modifications are carried out by human histone deacetylases (HDACs). Vorinostat (SAHA) is a known and registered anticancer drug, which inhibits human histone deacetylases. On the other hand, primaquine, a well-known antimalarial drug, has certain anticancer activity, especially against MCF-7 cell line [1]. That prompted us to design sahaquines, primaquine-SAHA conjugates, which could lead to potent anticancer activity against specific cancer cell lines. To fully test our hypothesis, the following features were varied: the length and type of the linker between PQ and hydroxamic acid moiety, as well as the substitution of the hydroxamic acid moiety, leading to 4 different classes of derivatives. The cytostatic activities of synthesized compounds were tested on four different human cancer cell lines: glioblastoma (A1235), hepatocellular carcinoma (Hep G2), breast adenocarcinoma (MCF-7) and osteosarcoma (U2OS), while the potential toxicity was tested on human kidney cell line HEK-293. In both tests results were compared with primaquine and a registered cytostatic agent cisplatin. Compound 5b was shown to be the most active against MCF- 7 (IC50 0.8 ± 0.4 µM), while other compounds had IC50 ranging from 3.9 ± 1.5 µM to 16.6 ± 0.8 µM. Against Hep G2, none of the tested compounds showed high activity, 4d being the most potent (IC50 9.9 ± 1.1 µM). Activity against U2OS varied much: 5b and 4e showed strong activity (IC50 3.30 ± 0.05 µM and 7.1 ± 1.2 µM, respectively), while other compounds showed moderate activity, 3c being the least active (IC50 33.8 ± 2.9 µM). Derivatives 5b and 5d showed strong activity against A1235 (IC50 3.5 ± 0.7 µM and 6.8 ± 0.1 µM, respectively). All compounds were found to be less toxic than primaquine and cisplatin when tested on HEK- 293.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Farmacija

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