Synthesis, Characterization and Biological Activities of Tolfenamic Acid Alkaline Earth Metal Complexes

ABSTRACT Solid complexes of tolfenamic acid (tolfH) with Mg(II), Ca(II), Sr(II), and Ba(II) have been synthesized and characterized by CHN, metal contents analysis, FTIR, UV, 1 H‐NMR spectroscopy, thermal (TGA, DTG, DTA, and DSC) analysis, molar conductance, powder X‐ray diffraction (XRD), and scanning electron microscopy (SEM–EDX). Based on these studies, the probable formulae for the complexes are [Mg(tolf)Cl(H 2 O) 3 ].4H 2 O, [Ca(tolf) 2 (H 2 O) 2 ], [Sr 2 (tolf) 4 (H 2 O) 4 ], and [Ba 2 (tolf) 4 (H 2 O) 4 ]. The ligand tolfenamate ion (tolf) exhibited different modes of coordination, including bidentate and chelating. The 1 H‐NMR displayed the presence of tolfenamato ions in the coordination sphere, the purity and stability of the complexes in solution. The average crystallite sizes of the complexes were determined by XRD and ranged from 55 to 70 nm. SEM micrographs showed the rod‐ or plate‐like morphology of the prepared complexes. The complexes showed promising antioxidant activity in the DPPH radical scavenging method, with an IC 50 value of 12–15 μg/mL. Against gram‐positive and gram‐negative bacteria, as well as fungi, the metal complexes also demonstrated significant antimicrobial activity. In the brine shrimp lethality bioassay, the metal complexes exhibited significantly highest cytotoxicity with the range of 15.25–24.57 μg/mL. All the complexes showed cytotoxicity against human cervical carcinoma HeLa cell lines, while the ligand itself did not show any cytotoxicity to these cancer cells. Furthermore, the metal complexes exhibited improved central and peripheral analgesic activity compared to tolfenamic acid.