Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: Synthesis and antimalarial evaluation

We describe the synthesis and antimalarial activities of 1H-1,2,3-triazole tethered 7-chloroquinoline-isatin hybrids. Activity against cultured parasites was dependent on the C-5 substituent of the isatin ring as well as the alkyl chain length between the isatin and 7-chloroquinoline moieties. Compound 8h, with an optimum alkyl chain length (n = 3) and a chloro substituent at the C-5 position of the isatin ring, displayed the best activity among the test compounds, with IC50 value of 1.21 μM against cultured W2-strain Plasmodium falciparum.

Fifteen 7-chloroquinoline-isatin conjugates have been synthesized and evaluated for their antiplasmodial profile. The compound 8h with an optimum combination of longer alkyl chain length and chloro substituent at C-5 position of isatin ring displayed the best activity among the test compounds.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis of 7-chloroquinoline-isatin hybrids via azide-alkyne cycloaddition.
► Antiplasmodial activity of synthesized hybrids was evaluated against W2 strain.
► Activity dependence on the C-5 substituent of isatin ring and the length of alkyl chain.