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

Abstract

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.