Design, synthesis, and histone deacetylase inhibition study of novel 4-(2-aminoethyl) phenol derivatives.

Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4-(2-aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug-like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π-stacking, Zn2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4-(2-aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4-(2-aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target-specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future.

A validated chiral chromatographic method for the enantiomeric separation of acalabrutinib.

Acalabrutinib is aided in the treatment of various cancers, which acts by inhibiting Bruton tyrosine kinase. Acalabrutinib belongs to the imidazopyrazine class consisting of a chiral carbon, resulting in two enantiomers. Currently, no methods exist for the separation and quantification of these enantiomers. A novel and selective enantiomeric chromatographic technique has been established to estimate the enantiomeric purity of acalabrutinib. Chiral separation was carried out on an immobilized amylose-based chiral stationary phase with methyl tert-butyl ether/ethanol/ethylenediamine (60:40:0.1% v/v) mixture as a mobile phase. The total runtime is 20 min, and the resolution (Rs ) between the enantiomers was more than 2.5. The detection and quantification thresholds for the R-enantiomer were 0.06 and 0.2 µg mL-1 , respectively, for a test concentration of acalabrutinib (1000 µg mL-1 ). The linearity of the technique for the R-enantiomer was excellent (R2 > 0.999) over the range from the limit of quantification to 0.3%. Recovery of the R-enantiomer was ranged from 95% to 102%, indicating the greater accuracy of the technique. For a 48-h research period, the drug was shown to be stable.