2nd generation of harmicines as potential antiplasmodial agents (CROSBI ID 678538)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Perković, Ivana ; Poje, Goran ; Rajić, Zrinka
hrvatski
2nd generation of harmicines as potential antiplasmodial agents
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.
malaria, antiplasmodial activity, harmine, cinnamic acid, synthesis
nije evidentirano
engleski
2nd generation of harmicines as potential antiplasmodial agents
nije evidentirano
malaria, antiplasmodial activity, harmine, cinnamic acid, synthesis
nije evidentirano
Podaci o prilogu
109-109.
2019.
nije evidentirano
objavljeno
Podaci o matičnoj publikaciji
11th Joint Meeting on Medicinal Chemistry, Book of Abstracts
Podaci o skupu
11th Joint Meeting on Medicinal Chemistry 2019
poster
27.06.2019-30.06.2019
Prag, Češka Republika