Solvent-driven structural adaptation in a novel anticancer sulfonamide chalcone

Abstract

Investigation of multiple crystal forms of a substance and how these forms influence their properties are of great importance to the medicinal chemistry field, impacting strongly on the discovery of new drugs such as anticancer agents. Specifically, some chalcones and sulfonamides have been reported as anticancer agents. However, since such biological activity is related to both molecular structure and supramolecular arrangement, understanding the role of possible forms of a compound is of great importance. In this paper, a novel sulfonamide chalcone (E)-2,5-dichloro-N-(3-(3-(3-nitrophenyl)acryloyl)phenyl) benzenesulfonamide was prepared and obtained as two different crystal forms, a multicomponent one crystallized together with acetone (I) and a single component one exhibiting conformerism named (II). The influence of acetone in the supramolecular arrangement of these two crystal forms was evaluated through single crystal X-ray diffraction, Hirshfeld surfaces and thermal analysis. The crystal packing of both molecules is stabilized by the interactions Csingle bondH⋯O, Nsingle bondH⋯O and Csingle bondH⋯Cl. In I, acetone molecules are responsible for binding two dimer chains, while in II the solvent space is substituted by voids on refinement. In addition, the presence of solvent molecules was confirmed by differential thermal analysis and thermogravimetry profile as an exothermic peak starting at 108 °C. There was proximity of the cytotoxicity of I and II against three human tumor cell lines in GI% values (SF-295 ≈ 92.74 ± 4.46; PC-3 ≈ 97.33 ± 0.51; and HCT-116 ≈ 100.57 ± 0.32). We suggest that the multiple crystalline forms do not influence the anticancer activity of the sulfonamide chalcone studied.