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Normal‐phase and reversed‐phase high‐performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)‐enantiomer impurity have been developed on the cellulose‐based Chiralcel OJ‐H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol–water–diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)‐enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 μg mL−1, respectively.

Wingless/integrase-11 (WNT)/β-catenin pathway is a crucial upstream regulator of a huge array of cellular functions. Its dysregulation is correlated to neoplastic cellular transition and cancer proliferation. Members of the Dishevelled (DVL) family of proteins play an important role in the transduction of WNT signaling by contacting its cognate receptor, Frizzled, via a shared PDZ domain. Thus, negative modulators of DVL1 are able to impair the binding to Frizzled receptors, turning off the aberrant activation of the WNT pathway and leading to anti-cancer activity. Through structure-based virtual screening studies, we identified racemic compound RS4690 (1), which showed a promising selective DVL1 binding inhibition with an EC50 of 0.74 ± 0.08 μM. Molecular dynamic simulations suggested a different binding mode for the enantiomers. In the in vitro assays, enantiomer (S)-1 showed better inhibition of DVL1 with an EC50 of 0.49 ± 0.11 μM compared to the (R)-enantiomer. Compound (S)-1 inhibited the growth of HCT116 cells expressing wild-type APC with an EC50 of 7.1 ± 0.6 μM and caused a high level of ROS production. These results highlight (S)-1 as a lead compound for the development of new therapeutic agents against WNT-dependent colon cancer.

A direct enantio‐ and chemo‐selective high‐performance liquid chromatography method was developed for separating the enantiomers of the pain medicine tramadol and its O‐desmethyl active metabolite in a single run. The simultaneous separation was achieved on the immobilized‐type amylose tris(3‐chloro‐5‐methylphenylcarbamate) chiral stationary phase. The method was optimized in normal‐phase and reversed‐phase using ethanol as an organic modifier. It was demonstrated that ethanol is a valid alternative to the predominant high‐performance liquid chromatography solvents in use for the preparation of reversed‐phase eluents such as methanol and acetonitrile. With the green mobile phase ethanol‐water‐diethylamine, 80:20:0.1 (v/v/v) the limits of quantification for the (+)/(‐)‐enantiomers of tramadol and its O‐desmethyl active metabolite were 1.14/1.16 and 1.33/1.40 μg mL–1, respectively.

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