Naslov
New primaquine amides with halogenphehyl substituents as potential cytostatic agents

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

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

Izvornik
4th EFMC Young Medicinal Chemist Symposium / - , 2017, 103-103

Skup
4th EFMC Young Medicinal Chemist Symposium

Mjesto i datum
Austrija, 31.08.2017. - 01.09.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
primaquine, amide, halogenphenyl substituents, cytostatic agent

Sažetak
Despite enormous human efforts in the field of oncology and anticancer drugs, cancer remains one of the leading causes of death worldwide [1]. Novel and more efficient therapies, as well as drugs with new mechanisms of action are desperately needed. Several antimalarial drugs, including primaquine (PQ) and chloroquine, exert antitumoral activity and are currently being evaluated in the clinical trials [2]. Design, synthesis and cytostatic evaluation of PQ derivatives was in the centre of our research efforts for almost a decade [3]. Recently, we have reported synthesis and biological activity of urea and bis-urea primaquine derivatives with hydroxyphenyl or halogenphenyl substituents (1a- f, Scheme), which exerted strong antiproliferative activity against various types of tumour cell lines, with significant selectivity towards breast cancer cell line, MCF-7 [4]. On the basis of that finding, our group has recently synthesized new primaquine amides bearing halogenphenyl substituents 2a-f, with the simplified linker between PQ and halogenphenyl substituents (ethane instead of bis-amide bridge, Scheme). The aim of this work was to further explore the role of the linker between PQ and substituted aniline and to prepare new PQ amides with halogenphenyl substituents 3a-f and ethylene instead of ethane bridge. Presence of the double bond dictates more sterically rigid compounds in the comparison to amides 2. Synthetic pathway to PQ derivatives 3a-f involves three steps: coupling of PQ with monoethyl fumarate, hydrolysis of the obtained ethyl ester, and coupling of the carboxylic acid with meta- or para- monosubstituted aniline derivatives (F, Cl, CF3). In both cases, coupling was achieved by the stardard coupling conditions (HATU, DIEA, DCM). Structures of the final compounds were confirmed by 1H and 13C NMR, IR and MS. Cytostatic evaluation on a panel of cancer cell lines is in progress.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA