Synthesis, characterization, enzyme inhibition, antioxidant, anticancer and antimicrobial potential of organotin(IV) derivatives of 4-fluorophenoxyacetic acid

Abstract

Five organotin(IV) derivatives (1–5) of general formula R3SnL and R2SnL2, where R = C4H9 {1, and 3}, CH3 {2 and 4}, C6H5 {5} and L represents 4-fluorophenoxyacetate ligand were synthesized by the condensation reaction of corresponding organotin(IV) chloride and sodium-4-fluorophenoxyaceate salt in dry chloroform under reflux condition. The elemental analysis has confirmed the expected composition of the complexes. The Δν values (less than 200 cm−1) calculated from FT-IR spectra revealed bridging/chelating bidentate coordination of the carboxylate ligand to the tin. The single crystal XRD analysis has shown polymeric chain structures for complexes 1 and 2 with bridging bidentate carboxylate ligand connecting tin atoms having trigonal bipyramidal geometry. In complex 3, the tin atom with chelating anisobidentate ligands adopted a highly distorted octahedral geometry. Quantum chemical studies have shown a good correlation between experimental and theoretically calculated geometric parameters. The Hirshfeld surface and fingerprint plots calculations have shown H…H interactions as the major intermolecular contacts present within the crystal structures of complexes 1–3. The experimental and simulated (1H and 13C) NMR spectra were found to be in good agreement. The in vitro enzyme inhibition {acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase B (MAO-B), alpha-glucosidase, dipeptidyl peptidase-4, cyclooxygenase (COX) and lipoxygenase (LOX)}, antioxidant [DPPH = 2,2-diphenyl-1-picrylhydrazyl and ABTS = 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid] and antileishmanial assays have shown dose dependent responses of the test compounds. Complexes have shown higher activities compared to the free ligand acid. Complexes were particularly more active acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors, especially complex 3 (IC50 = 0.60 µg/mL) was even more potent than the standard drug Galantamine (IC50 = 2.82 µg/mL). MTT [MTT= (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide tetrazolium)] assay showed potent anticancer activity for complex 4 (IC50 = 12.54 ± 0.19 µg/mL), complex 5 (IC50 = 16.44 ± 0.17 µg/mL), and free 4-fluorophenoxyacetic acid (HL) (IC50 = 21.95 ± 0.09 µg/mL) among the tested compounds towards the brain cancer cell line (Malignant glioma U87). The nonmalignant human embryonic kidney HEK293 cells were found to be less vulnerable to the test compounds. In the antimicrobial assays, complexes 1 and 2 have shown activities higher than the standard drug Cefixime against C. albicans and P. aeruginosa, respectively.

Keywords

• Organotin(IV) carboxylates
• Crystal Structures
• Anti-inflammatory
• Antidiabetic
• Anti-Alzheimer
• Antioxidant