Exploring Titanium(IV) Complexes as Potential Antimicrobial Compounds.

Israel Rodríguez,Branlee Sang,Arthur D Tinoco,Andrea N Maser-Figueroa,Lauren Fernández-Vega,Patricia González-Pagán

doi:10.3390/antibiotics11020158

Israel Rodríguez, Branlee Sang + Show 4 more

Open Access

https://doi.org/10.3390/antibiotics11020158

Copy DOI

Journal: Antibiotics	Publication Date: Jan 26, 2022
Citations: 7	License type: CC BY 4.0

Affiliation: University of Puerto Rico at Río Piedras

Abstract

Due to the rapid mutation of pathogenic microorganisms, drug-resistant superbugs have evolved. Antimicrobial-resistant germs may share their resistance genes with other germs, making them untreatable. The search for more combative antibiotic compounds has led researchers to explore metal-based strategies centered on perturbing the bioavailability of essential metals in microbes and examining the therapeutic potential of metal complexes. Given the limited knowledge on the application of titanium(IV), in this work, eight Ti(IV) complexes and some of their corresponding ligands were screened by the Community for Open Antimicrobial Drug Discovery for antimicrobial activity. The compounds were selected for evaluation because of their low cytotoxic/antiproliferative behavior against a human non-cancer cell line. At pH 7.4, these compounds vary in terms of their solution stability and ligand exchange lability; therefore, an assessment of their solution behavior provides some insight regarding the importance of the identity of the metal compound to the antimicrobial therapeutic potential. Only one compound, Ti(deferasirox)2, exhibited promising inhibitory activity against the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and minimal toxicity against human cells. The ability of this compound to undergo transmetalation with labile Fe(III) sources and, as a consequence, inhibit Fe bioavailability and ribonucleotide reductase is evaluated as a possible mechanism for its antibiotic effect.

Highlights

The urgent need for new classes of antimicrobial drugs to fight resistance and the evolution of superbugs has forced researchers to explore different strategies
Given the central role that essential metals can play in microbial growth and the distinctive chemistry that can be facilitated by metals coupled with the varied structures and properties that they can adopt from ligand complexation, metal-centered antimicrobial strategies are an exciting new research avenue
Ti(IV) compounds (Figure 1) selected for submission to the Community for Open Antimicrobial Drug Discovery (CO-ADD) antimicrobial screening had to meet the criteria of low antiproliferative activity/cytotoxicity against a non-cancer human cell line as measured by the MTT assay at pH 7.4

Summary

Introduction

The urgent need for new classes of antimicrobial drugs to fight resistance and the evolution of superbugs has forced researchers to explore different strategies. The classical approach has been the synthesis of derivatives of already known compounds that can attack microbes rather than human cells, the majority of which are purely organic compounds This approach is quickly reaching the limit of its possibilities. One approach is developing compounds that can uniquely perturb the essential metal homeostasis within pathogenic microbes and possibly even attenuate their bioavailability [1,2,3,4]. Another approach is assessing the therapeutic potential of metals in ion or complex form. A recent review highlights some of the most important antibiotic metal complexes developed over the last decade [14]

Methods

Results

Discussion

Conclusion