Naslov
Harmiquins, novel potent antiplasmodial hits

Autori
Rajić, Zrinka ; Poje, Goran ; Pessanha de Carvalho, Lais ; Held, Jana ; Perković, Ivana ; Tandarić, Tana ; Vianello, Robert

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

Izvornik
9th BBBB International Conference on Pharmaceutical Sciences, Book of Abstracts / Obreza, Aleš ; Dreu, Rok ; Zvonar Pobirk, Alenka ; Sterle Zorec, Barbara - Ljubljana : Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo, 2022, 224-225

Skup
9th BBBB International Conference on Pharmaceutical Sciences Pharma: Sciences of Tomorrow

Mjesto i datum
Ljubljana, Slovenija, 15.09.2022. - 17.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
harmine ; chloroquine ; hybrid molecules ; synthesis ; antiplasmodial activity ; PfHsp90

Sažetak
Here we present design and synthesis of AT and TT harmiquins, evaluation of their biological activity and possible mechanism of action. Harmiquins displayed remarkable activity against the erythrocytic life stage of CQsensitive, as well as CQ-resistant Plasmodium strains. The most active compound, AT harmiquine 32, displayed a 5.5-fold higher activity against Pf3D7 than CQ (IC50 = 2 ± 0.3 nM), at least 15.9-fold higher activity than CQ against P. falciparum CQ resistant strains and had a very high selectivity index (4450). Two possible mechanisms of action, inhibition of heme polymerisation and binding to PfHsp90, might play a role in the inhibition of Plasmodium intraerythrocytic development.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA