Synthesis and antiplasmodial evaluation of novel mefloquine-based fumardiamides

Znanstveni rad - Izvorni znanstveni rad

• Autor: Maja Beus
• Autor: Diana Fonthina
• Autor: Jana Held
• Autor: Zrinka Rajić
• Autor: Miguel Prudencio
• Autor: Branka Zorc
• Autorova ustanova: Sveučilište u Zagrebu; Farmaceutsko-biokemijski fakultet; (Zavod za farmaceutsku kemiju)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Farmacija; Farmacija

Sažetak (engleski)

The paper is focused on the synthesis and screening of the antiplasmodial activity of novel fumardiamides 5–10 with the mefloquine pharmacophore and a Michael acceptor motif. Multi-step reactions leading to the title compounds included two amide bond formations. The first amide bond was achieved by the reaction of (E)-ethyl 4-chloro-4-oxobut-2-enoate (1) and N1-(2,8-bis(trifluoromethyl)quinolin-4-yl)butane-1,4-diamine (2). The obtained ester 3 was hydrolysed and gave acid 4, which then reacted with the selected halogenanilines in the presence of HATU/DIEA and formed products 5–10. Title compounds showed marked, dose dependent activity in vitro against hepatic stages of Plasmodium berghei. IC50 values of the most active compounds 5, 7 and 9 bearing 3-fluoro, 3-chloro and 3-trifluoromethyl substituents were 3.04–4.16 µmol L–1, respectively. On the other hand, the compounds exerted only weak activity against the erythrocytic stages of two P. falciparum strains (Pf3D7 and PfDd2) in vitro, with the exception of compound 5 (IC50 = 2.9 µmol L–1).

• Ključne riječi (engleski): mefloquine; 2,8-bis(trifluoromethyl)quinoline; fumardiamide; halogenaniline; antiplasmodial activity
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran - međunarodna recenzija
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: Acta Pharmaceutica
• Brojčani podaci: vol. 69, br. 2, str. 233-248
• p-ISSN: 1330-0075
• e-ISSN: 1846-9558
• DOI: https://doi.org/10.2478/acph-2019-0019
• URN:NBN: urn:nbn:hr:163:062541
• Datum objave publikacije: 2019
• URL dokumenta: https://hrcak.srce.hr/217028
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2019-03-08 16:22:52