Docking studies. To investigate the possible binding mode of 18b, we performed docking experiments with PfHDAC1 and, since 18b showed also nanomolar inhibition of hHDAC1 we docked 18b also into hHDAC1. Since there is no published crystal structure of PfHDAC1 so far, we used a previously published homology model of PfHDAC1, which is based on a hHDAC2 crystal structure (PDB ID: 5IWG). To compare the two distinct enantiomers of 18b, we performed docking experiments with both (R)-18b and (S)-18b. Both (R)-18b and (S)-18b were predicted to occupy the PfHDAC1 L1 pocket, enabling interactions of the benzylic cap group within this pocket (Figure ). Docking studies of 18b with hHDAC1 (PDB ID: 5ICN) revealed slightly different binding modes. The cap groups of both enantiomers are pointed towards the L1 loop. However, contrary to PfHDAC1 the pyrrolidine moiety approaches the L1 pocket, while the benzyl moiety is slightly turned away from the L1 loop. The predicted binding modes of both enantiomers involve charged interactions between the positively charged pyrrolidine ammonium and Asp99 (Figure ). In comparison to hHDAC1, the L2 loop of PfHDAC1 seems to be slightly longer due to two additional amino acids (Ala95 and Thr96), which might influence the binding mode of 18b. Instead, it was predicted that Thr96 interacts with the benzyl residue of (R)-18b and (S)-18b via a CH-π interaction, whereas Asp97 was pointed away from the inhibitors (Figure ). Anticancer activity. The compound series was further evaluated for its anticancer activity using a cell viability (MTT) assay to assess the effects on solid cancer cell lines. Specifically, the tongue squamous cell carcinoma cell line Cal27 and the hepatocellular carcinoma cell line HepG2 were selected for these experiments. Additionally, to evaluate cytotoxicity against non-cancerous cells, the lung fibroblast cell line MRC-5 was included. The results from these cytotoxicity screenings are presented in Table .