Mechanochemical Assembly of Nalidixic Acid Bioinspired Metal–Organic Compounds and Complexes toward Improved Solubility

Abstract

Nalidixic acid is an antibiotic from the quinolones family whose bioavailability is limited due to its low solubility. The development of complexes and bioinspired metal−organic frameworks has been explored as a way to achieve controlled drug delivery and release, and we demonstrate that they can also be used to tune drugs' physicochemical properties, such as solubility. Herein we disclose a series of complexes and frameworks of nalidixic acid and Zn. One of these frameworks duplicates the solubility of nalidixic acid, and it is stable on the shelf and to 77% room humidity. The incorporation of a second ligand into the frameworks is also presented, showing the possibility to develop extended networks with further potential applications.

Supramolecular assembly of two copper(II) coordination compounds of topiroxostat with dialkylformamide ligands

“…Meanwhile, quite a few APIs could also serve as good candidates for constructing new complexes and further enrich the coordination chemistry and biochemistry [6]. To date, a variety of metal complexes were constructed from API-based organic ligands, such as norfloxacin [7], enoxacin [8], ofloxacin [9], letrozole [10], fluconazole [11], and nalidixic acid [12]. The resulting complexes may exhibit more enhanced biological properties in comparison with the pure API molecules.…”

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

“…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].…”