Naslov
2nd generation of harmicines as potential antiplasmodial agents

Autori
Perković, Ivana ; Poje, Goran ; Rajić, Zrinka

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

Izvornik
11th Joint Meeting on Medicinal Chemistry, Book of Abstracts / - , 2019, 109-109

Skup
11th Joint Meeting on Medicinal Chemistry 2019

Mjesto i datum
Prag, Češka Republika, 27.06.2019. - 30.06.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
malaria, antiplasmodial activity, harmine, cinnamic acid, synthesis

Sažetak
According to the World Malaria Report issued in 2018, malaria is responsible for 266 000 deaths of children aged under 5 years worldwide. In order to achieve the 2020 milestones of the Global Technical Strategy for malaria (a global reduction of at least 40% in malaria case incidence, mortality rates and elimination in at least 10 countries) substantial ammount of funding and research is required.1 Recent publications have revealed that harmine, a naturally occurring β-carboline is a selective inhibitor of a malaria parasite Plasmodium falciparum heat shock protein 90 (PfHsp90), which has been identified as as valuable target antimalarial therapy.2 This work represents a continuation of our efforts in pursuit for novel antimalarial leads. Recently we have reported design and synthesis of harmicines, hybrids comprising harmine and cinnamyl moiety. In order to expand our library of harmicines, we have decided to modify harmine at the position 3 of the β-carboline ring where hydroxymethylene group was introduced. The 2nd generation of harmicines was derived from L-tryptophan methyl ester. Microwave assisted Pictet-Spengler reaction, followed by oxidation, was used for the construction of the β-carboline 2.3 Next, reduction of an ester gave alcohol 3. The treatment of alcohol with propargyl bromide in the presence of Cs2CO3 in DMF resulted in N-alkylation at the position 9 of β-carboline ring. Finally, Cu(I) catalyzed azide-alkyne cycloaddition between alkyne 4 and various cinnamyl azides gave target compounds 5 (Fig. 1). Evaluation of antiplasmodial activity is in progress.

Izvorni jezik
Hrvatski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA