Hydrogen-bond-driven supramolecular helical assembly of a coumarin-substituted phthalonitrile derivative: synthesis and in vitro anticancer activity against colorectal adenocarcinoma

Abstract

Phthalonitrile derivatives are generally reported to crystallize in space groups P21/c and P 1 in the literature. In this study, 7-hydroxy-4,8-dimethyl-3-pentylcoumarin (2) and its phthalonitrile derivative (2d) were crystallized; 2d crystallized in the rare trigonal space group R 3. In the phthalonitrile derivative (2d), weak C—H...O hydrogen-bonding interactions promoted the formation of supramolecular double helices, and these supramolecular P and M double helices came together to form a honeycomb-like architectural motif involving one-dimensional tubular channels. In silico molecular-docking studies were performed to support the experimental processes and the results agree with each other. In vitro studies of compounds 2 and 2d were performed in LoVo colorectal adenocarcinoma and CCD18Co healthy human cell lines using flow cytometry. For compounds 2 and 2d, there was a statistically significant increase (p < 0.001) in both early and late apoptosis with respect to the control in a dose-dependent manner.