Mg- and Mn-MOFs Boost the Antibiotic Activity of Nalidixic Acid

Abstract

The development of metal–organic frameworks (MOFs) enclosing active pharmaceutical ingredients is of considerable interest, as their use in controlled drug release and delivery is very promising. Although nalidixic acid is an antibiotic with a broad spectrum of biological applications, effective mainly against Gram-negative infections, its oral bioavailability is low due to a poor solubility and slow dissolution. Herein, we report new metal–organic frameworks (BioMOFs) comprising nalidixic acid and divalent magnesium and manganese ions. These compounds showed an adequate cytotoxicity and improved antimicrobial activity, especially against Gram-negative bacteria. These BioMOFS are among the first examples containing active pharmaceutical ingredients as linkers. Importantly, it is shown that a remarkable increase of the antimicrobial activity of certain antibiotics may be achieved by delivering them in the form of BioMOFs.

Recent Bio-Advances in Metal-Organic Frameworks

“…More recently, Mg-and Mn-based MOFs were synthesised using the antibiotic agent nalidixic acid [89]. Nalidixic acid is an antibiotic with high bactericidal and bacteriostatic activity against Gram-negative bacteria, yet its low aqueous solubility leads to poor oral bioavailability [90,91].…”

Antimicrobial Activity of Pyrazinamide Coordination Frameworks Synthesized by Mechanochemistry

“…MOFs with biocompatible composition were reported to be viable drug carriers to overcome some of the problems related to drug delivery [ 9 , 20 , 21 , 22 ]. In particular, MOFs designed using antibiotics as ligands to yield antibiotic coordination frameworks (ACFs) were proposed to improve the antimicrobial activity [ 23 , 24 , 25 ], as well as the physicochemical properties of the antibiotics [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Bioactivity of Isostructural Hydrogen Bonding Frameworks Built from Pipemidic Acid Metal Complexes

“…Calcium is an abundant metal in the human body and it is vital in several cellular physiological and biochemical processes, such as signal transduction pathways [38], enzyme cofactor [39] and intercellular contacts [40]. Manganese is essential for bone strength but is also involved in enzymatic reactions such as the detoxification of superoxide free radicals in biological systems [21,41]. Zinc is an important trace metal in human nutrition that is crucial for many physiological functions and is involved in several enzyme actions in biological systems [42,43].…”

“…The coordination of quinolones to biocompatible metals is of considerable interest from biological and pharmaceutical point of views and it has been shown to be an alternative approach to obtain compounds with improved antimicrobial activity while simultaneously altering their physicochemical characteristics [18,19]. Our group has proven that bio-inspired metal-organic frameworks of nalidixic acid, the first quinolone antibiotic, have increased solubility and bioactivity compared to the free antibiotic [20,21]. Efthimiadou et al studied the antimicrobial activity of several pipemidic acid complexes, as well as their interaction with calf-thymus (CT) DNA with diverse spectroscopic techniques, and showed that the complexes are able to bind to DNA; in all the complexes, a B → A CT DNA transition is detected [22].…”