Ga(III) Pyridinecarboxylate Complexes: Potential Analogues of the Second Generation of Therapeutic Ga(III) Complexes?

Overview

Journal J Biol Inorg Chem

Publisher Springer

Specialty Biochemistry

Date 2023 Jul 27

PMID 37498326

Authors

Michaela Rendosova

Robert Gyepes

Simona Sovova

Danica Sabolova

Maria Vilkova

Petra Olejnikova

Martin Kello

Boris Lakatos

Zuzana Vargova

Affiliations

Soon will be listed here.

Abstract

A series of novel Ga(III)-pyridine carboxylates ([Ga(Pic)]·HO (GaPic; HPic = picolinic acid), HO[Ga(Dpic)]·HO (GaDpic; HDpic = dipicolinic acid), [Ga(Chel)(HO)(OH)]·4HO (GaChel; HChel = chelidamic acid) and [Ga(Cldpic)(HO)(OH)] (GaCldpic; HCldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-HDpic systems by potentiometry and H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)] (logβ = 16.23(6)), [Ga(Pic)] (logβ = 20.86(2)), [Ga(Dpic)] (logβ = 15.42(9)) and [Ga(Dpic)(OH)] (logβ = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.

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