Design and synthesis of harmine and coumarin/quinoline hybrids bridged with 1, 2, 3-triazole (CROSBI ID 673583)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Raić-Malić, Silvana ; Perković, Ivana ; Rajić, Zrinka
engleski
Design and synthesis of harmine and coumarin/quinoline hybrids bridged with 1, 2, 3-triazole
Malaria, one of the neglected tropical diseases, is responsible for more than 430000 deaths and 210 million new cases annually. The cause of malaria, protozoal parasite of the genus Plasmodium, is developing resistance to the known drugs, which drives the need for the discovery and development of new antimalarials. One of the methods for finding new drug entities is to covalently combine two pharmacophores in one molecule, i.e. to prepare hybrid drugs. Thus, we decided to employ that concept in the present study, in which we have designed and prepared hybrids based on -carboline alkaloid harmine and coumarine or quinoline, linked with 1, 2, 3-triazole ring. It has been established that harmine and related b-carbolines exhibit antimalarial activity, possibly by inhibiting PfHSP90. On the other hand, coumarins are the most abundant naturally occurring secondary metabolites found in several plant families, microorganisms and a few animal species, while quinoline-containing antimalarial drugs, such as primaquine and chloroquine, are the mainstays of chemotherapy against malaria. In addition, coumarin and quinoline derivatives possess a broad spectrum of biological activities, including antimalarial, antibacterial and antifungal activity. 1H-1, 2, 3-triazole scaffold will be introduced by the means of Cu(I) catalyzed regioselective 1, 3-dipolar cycloaddition of terminal alkynes and organic azides („click“ reaction). It was chosen as a linker due to the high chemical stability and the ability to form hydrogen bonds with biomolecular targets. Triazoles are also recognized as bioisosters of amides. Harmine and 7-O-demethylated harmine (harmole) were converted to the corresponding alkynes 1, 6 and 7 by the means of propragylation, while 4-chlorocoumarine and 4, 7-dichloroquinoline were transformed to the appropriate azides 2 and 3, respectively. Finally, “click” reaction between an alkyne and an azide produced conjugates 4, 5 and 8-11. Evaluation of the antimalarial activity on both erythrocytic and hepatic stages is in progress.
harmine, malarina, quinoline, coumarin, hybrid drugs
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Podaci o prilogu
43-44.
2019.
objavljeno
Podaci o matičnoj publikaciji
Kinney, Bill ; Reynolds, Charles H.
Nassau: Fusion Conferences Limited
Podaci o skupu
4th Drug Discovery Re-Invented Conference
poster
21.02.2019-24.02.2019
Nassau, Bahami