In this work, we aimed to efficiently and rapidly synthesize different chemotypes derived from quisinostat to investigate their antiplasmodial and anticancer potential. To achieve this, we applied multicomponent reactions (MCRs). These reactions offer several advantages, including rapid product 0.062 µM against Dd2. Overall, type B inhibitors demonstrated reduced activity against P. falciparum in comparison to type A compounds, with IC50 values ranging from 0.10 to 0.23 µM for 3D7 and from 0.13 to 0.29 µM for Dd2. The HDAC inhibitors of type C turned out to have similar activity against the tested parasite lines as type B, except for 18b (IC50 (3D7) = 0.023 µM; IC50 (Dd2) = 0.047 µM) and 18f (IC50 (3D7) = 0.071 µM; IC50 (Dd2) = 0.069 µM). These two inhibitors share two key structural elements: the cyclic amine (Y = NH) and the formyl residue at the tertiary amide (R 2 = H). Additionally, the benzyl residue at R 1 seems to be slightly favourable for antiplasmodial activity (see 18b vs 18f, and 18c vs 18d), with the exception of 18e, which showed similar activity as the benzyl derivative 18c.