Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro

Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the need for the development of new antimalarial drugs. Synthesis and in vitro antiplasmodial evaluation of t...

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Published in:	Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 17; no. 8; p. 820
Main Authors:	da Silva Santos, Lucas, de Carvalho, Matheus Fillipe Langanke, de Souza Pinto, Ana Claudia, da Fonseca, Amanda Luisa, Dias Lopes, Julio César, de Pilla Varotti, Fernando, de Freitas, Rossimiriam Pereira, Alves, Rosemeire Brondi
Format:	Journal Article
Language:	English
Published:	Netherlands 01-01-2021
Subjects:	Antimalarials - chemical synthesis Antimalarials - chemistry Antimalarials - pharmacology Coumarins - chemical synthesis Coumarins - chemistry Coumarins - pharmacology Humans Isocoumarins - chemical synthesis Isocoumarins - chemistry Isocoumarins - pharmacology Molecular Structure Parasitic Sensitivity Tests Plasmodium falciparum - drug effects Structure-Activity Relationship Triazoles - chemical synthesis Triazoles - chemistry Triazoles - pharmacology 1 Plasmodium falciparum 2 Isocoumarin 3 4-dihydroisocoumarin antiplasmodial activity 3-triazole malaria
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Summary:	Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the need for the development of new antimalarial drugs. Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocoumarins and a 3,4-dihydroisocoumarin. The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4- dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an unprecedented connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant and sensitive strains (W2 and 3D7, respectively). Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of 25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89 μM and 0.85-2.07 μM against W2 and 3D7 strains, respectively. This study demonstrated the great potential of isocoumarin or 3,4-dihydroisocoumarin derivatives because practically all the tested substances were active against Plasmodium falciparum.
ISSN:	1875-6638
DOI:	10.2174/1573406416666200602161047