Supramolecular Gels Derived from Primary Ammonium salts of Naproxen and its Amino Acid Derivatives: Design, Synthesis, Structures and its Application as Anti-cancer Agent Against Melanoma Cell B16-F10.

Abstract

Supramolecular synthon approach was employed to develop a self-drug-delivery system based on organic salt based supramolecular gelators. One such key gelator NAP-PHE∙PEA derived from naproxen-phenylalanine conjugate and phenethylamine showed ability to gel both water and organic solvents. Supramolecular interactions such as π-π and C-H…π were probed by variable-temperature 1H-NMR spectroscopy in the hydrogelation process of NAP-PHE∙PEA. Single crystal structures of nine out of twelve salts were determined and the supramolecular synthon present therein was carefully analyzed. Intriguing insights of the gel-network structure was also investigated by structure-property correlation based on single-crystal and powder X-ray diffraction analysis of gelator/nongelator salts. The gelator salt NAP-PHE∙PEA displayed significant anti-cancer property against cancer cells (B16-F10. HeLa and A375); it was found non-cytotoxic against normal cell lines (E.derm and HEK-293) at comparable concentrations as revealed by MTT assays. The gelator salt NAP-PHE∙PEA also displayed significant anti-cancer behaviour against B16-F10 (scratch assay) and HeLa (multi-cellular tumour spheroid). The methyl salicylate gel of NAP-PHE∙PEA displayed shape-sustaining, load-bearing, self-healing properties along with rheoreversibility, which are considered important for topical applications.