Kaur, PavneetSharma, PriyankaKumar, VinodSahal, DinkarKumar, Rakesh2024-01-212024-08-132024-01-212024-08-132022-10-2622286010.1016/j.molstruc.2022.134406https://kr.cup.edu.in/handle/32116/3257An operationally simple three-component coupling of tetrahydroisoquinoline (THIQ), aldehydes and indoles or indole-3-carboxylic acids has been achieved using chitosan-ionic liquid supported FeCl3 (chit-IL@FeCl3) as a recyclable heterogeneous catalyst. The developed waste-free approach provided rapid access to biologically important THIQ-indole hybrids without the use of any additive or ligand. The synthesized THIQ-indole hybrids were evaluated as antiplasmodial agents against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compounds 4b (most potent against Pf3D7) and 4g (most potent against PfINDO) showed IC50 values of 1.32 and 0.26 �g/mL respectively. Also, 4g showed strong cytocidal action against both rings and trophozoite stages. Furthermore, cytotoxic study against human liver HUH 7 cells revealed that the most potent compound 4g with an excellent resistance index of 0.07 is also relatively non-toxic. The results of this study suggest that THIQ-indole hybrids hold an enormous potential for developing new antimalarial agents with novel mechanism of action. � 2022 Elsevier B.V.en-USAntiplasmodialCytotoxicityHeterogeneous catalystHybrid moleculesIndoleMulticomponent reaction (MCR)TetrahydroisoquinolineArticlehttps://linkinghub.elsevier.com/retrieve/pii/S0022286022020555