Naslov
Synthesis and in vitro antiproliferative activity investigation of 3-Hydroxy-2- methylpyridin-4-one derivatives

Autori
Petrović Peroković, Vesna ; Car, Željka ; Opačak- Bernardi, Teuta ; Tomić, Srđanka

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

Izvornik
17th Tetrahedron Symposium - Challlenges in Biological, Bioorganic, Organic & Medicinal Chemistry / - , 2016

Skup
17th Tetrahedron Symposium - Challlenges in Biological, Bioorganic, Organic & Medicinal Chemistry

Mjesto i datum
Sitges, Španjolska, 28.06.2016. - 01.07.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
3-hydroxy-2-methylpyridin-4-one ; adamantyl ; synthesis ; antiproliferative in vitro study

Sažetak
In the last couple of decades heterocyclic N- substituted 3-hydroxy-2-methylpyridin-4-one based compounds have emerged as an important substructure found in many natural and synthetic biologically active materials.1 High selectivity towards trivalent metal cations, especially Fe(III), is the primary basis of a number of 3- hydroxypyridin-4-ones' biological activities. These compounds have high potential in the treatment of iron overload diseases, in various blood pathologies such as thalassemias and hemochromatosis as well as in the treatment of neurodegenerative diseases. Various positions on the pyridinone ring, especially nitrogen atom, can be easily modified which allows the rational design of these compounds and modulation of their specific physicochemical and biological properties. Adamantyl based compounds are used clinically primarily for the treatment of neurological conditions, as well as antiviral and antitumour agents. The bulky, hydrophobic adamantane group was shown to modulate the therapeutic activity of many experimental drugs and prodrugs by increasing their partition coefficients and also by varying their mechanism of action.2 In view of our ongoing interest in pyridinone group of compounds3, especially in their biological activity4, we report the synthesis and antiproliferative in vitro study of several N-aryl 3-hydroxy-2-methylpyridin-4-ones and their lipophilic adamantyl analogues. Cytotoxicity was tested on K562 and MCF7 cell lines and several potential candidates were identified. These compounds showed antiproliferative effect in both lines in and below micromolar concentration range. Mechanism of growth inhibition (apotosis and cell cycle distribution) was investigated for specific compounds based on their cytotoxycity and structure.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA