Naslov
Synthesis of novel amide-type harmisinins, hybrids based on β-carboline and artesunate scaffolds

Autori
Poje, Goran ; Klarić-Kukuz, Rea ; Rajić, Zrinka

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

Izvornik
Frontiers in Medicinal Chemistry 2023 / - Beč, 2023, 81-81

Skup
Frontiers in Medicinal Chemistry 2023

Mjesto i datum
Beč, Austrija, 03.04.2023. - 05.04.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
harmine, artesunate, hybrid molecules, synthesis, antiproliferative activity, antimalarial activity
(ecules, synthesis, antiproliferative activity, antimalarial activity)

Sažetak
Both cancer and malaria have high incidence rates and are leading causes of mortality worldwide. [1] Due to the increasing resistance to the known drugs, the research of new agents with anticancer and/or antimalarial properties is of great importance. [2] In this work, we applied the molecular hybridization approach to develop amide-type harmisinins, novel hybrid compounds based on scaffolds with pronounced anticancer and antimalarial properties, namely harmine and artesunate. The title compounds were prepared by a coupling reaction of commercially available artesunate and the corresponding b-carboline-based amines 3a-c, obtained by a multistep reaction pathway (Scheme). Hydrolysis of harmine’s ether group in acidic media gave harmol 1, which was alkylated with ethyl, propyl or isopropyl bromide, in the presence of Cs2CO3 to give ethers 2a-c, respectively. The ethers were further N-alkylated with BocNH(CH2)2Br in the presence of Cs2CO3, with subsequent removal of the Boc protecting group in HCl/MeOH to afford amines 3a-c. The coupling reactions were carried out using HATU/DIEA in CH2Cl2 and gave targeted amides in poor to moderate yields. The structures of the novel harmisinins 4a-c were confirmed by standard techniques (1H and 13C NMR, IR and MS). Evaluation of their antiplasmodial activity and cytotoxicity is in progress. Literature: [1] T. Ellis, E. Eze, B. T. Raimi-Abraham, Infect. Agents Cancer 2021, 16, 33. [2] G. Poje, M. Marinović, K. Pavić, M. Mioč, M. Kralj, L. Pessanha de Carvalho, J. Held, I. Perković, Z. Rajić, Int. J. Mol. Sci. 2022, 23, 9315. This work was fully supported by the Croatian Science Foundation under the project number UIP-2017-05-5160.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA