Rationally Developed Metallogelators Derived from Pyridyl Derivatives of NSAIDs Displaying Anti-Inflammatory and Anticancer Activities

Metal–ligand
coordination involving hydrogen-bond-functionalized
ligands was employed rationally to get an easy access to a series
of metallogelators derived from 3-pyridyl derivatives of nonsteroidal
anti-inflammatory drugs [e.g., ibuprofen, sulindac, and flurbiprofen
designated as 3-pyIBU, 3-pySUL, and 3-pyFLR, respectively] and biogenic metal centers [Zn­(II),
Cu­(II), Mn­(II), and Ag­(I)]. A total of 13 metallogels (MG1–MG13) were obtained by allowing the ligands
and the metal salts to react in dimethyl sulfoxide (DMSO)/water at
room temperature. A slightly different solvent system (DMSO/water/MeOH)
afforded four crystalline coordination complexes of 3-pyIBU, namely, [{Cu­(3-pyIBU)4(DMSO)2}­(NO3)2] (CC1), [{Ag­(3-pyIBU)2}­(BF4)] (CC2), [{Ag­(3-pyIBU)2}­(ClO4)] (CC3), and [{Cu­(3-pyIBU)4(CH3OH)2}­(OTf)] (CC4), which were fully
characterized by single-crystal X-ray diffraction. However, none of
these coordination complexes produced metallogelsthe results
corroborated well with the rationale, based on which the metallogelators
were obtained. Two selected metallogels (MG3 and MG9) could be leached out from the corresponding metallogels
to the bulk solvent to the extent of 51 and 59%, respectively after
24 h of incubation at 37 °C, indicating their plausible use in
topical application. Moreover, one of the selected metallogelators,
i.e., MG9, displayed anti-inflammatory response and was
able to inhibit the migration of highly aggressive human breast cancer
cells MDA-MB-231, suggesting its plausible use as anticancer agent.