Exploiting Urea-Carboxylate Synthon for Designing Supramolecular Topical Hydrogel via Simple Organic Salt Formation: Synthesis, Crystal Structures, and Anticancer Behavior against Melanoma B16–F10 Cells

A supramolecular synthon-based crystal engineering approach
was
adopted to design an exceptional class of gelators utilizing simple
organic salt formation between monocarboxylic acid drugs (NSAIDs and
5-fluorouracil acetic acid or 5F) and N,N′-bis(4-pyridyl)urea (4U)
reacted in 1:1 and 2:1 molar ratio, respectively. Among 14 salts,
6 turned to be aqueous gelators. In fact, 2_5F·4U, an organic salt formed by the combination of two molecules of 5F and one molecule of 4U having molecular weight
<300 produced a pure water gel. Single-crystal X-ray diffraction
performed with six salts indicated the presence of 1D H-bonding networks
and the characteristic supramolecular synthons as envisaged. Several in vitro assays showed that the salt 2_5F·4U effectively induced apoptotic death in skin melanoma B16–F10
cells. Along with excellent rheoreversibility, the 2_5F·4U hydrogel could be shaped into a highly stable shape-sustaining translucent
patch which could be placed on an adhesive tape for topical applications.
The biological studies and material properties proved the 2_5F·4U hydrogel to be a potential topically applicable anticancer agent,
highlighting the merits of the proposed rationale of designing supramolecular
therapeutic hydrogels reported herein.