Front Cover: Synthesis, Computational Docking Study, and Biological Evaluation of a Library of Heterocyclic Curcuminoids with Remarkable Antitumor Activity (ChemMedChem 18/2018)

Abstract

The Front Cover shows the microscope slides of colorectal cancer cells (DLD‐1) treated with two new indole‐based heterocyclic curcuminoids bearing SCN substituents [3‐thiocyanato‐indole‐5‐curcuminoid–BF2 adduct (4‐BF2) on the left and (1E,4E,6E)‐5‐hydroxy‐1,7‐bis(3‐thiocyanoindole‐4)hepta‐1,4,6‐trien‐3‐one (5) on right] at 10 μM concentrations for 24 h. For comparison, the center slide shows cells treated with DMSO alone (control) for 24 h. Heterocyclic CUR‐BF2 compounds, such as indole‐4‐curcuminoid‐BF2 adduct (3‐BF2) shown in the center pose, exhibit favorable docking ability into Bcl‐2. Hydrophobic contacts between the atoms of the ligand and protein residues are the principle interactions involved, along with hydrogen bond interactions between F and N ligand atoms and hydrogen bond donor groups in neighboring protein residues. The DFT‐optimized structures of two remarkably active bis‐SCN‐substituted CUR‐BF2 compounds are displayed as well. Unlike the very distinct yellow color of curcumin itself, these new heterocyclic analogs have distinctly different colors. More information can be found in the Full Paper by Kenneth K. Laali et al. on page 1895 in Issue 18, 2018 (DOI: 10.1002/cmdc.201800320).