A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic Acid

Abstract

Novel ionic liquids and organic salts based on mono-o rd ianionic zoledronate and protonated superbases, choline and nalkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Amongt he zoledronate-basedi onic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C 3 OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skinf ibroblast cells. Because osteosarcoma is a bone pathologyc haracterized by an increase in bone turnover rate, the resultsp resented herein may be ap romising starting point for the development of new ionic pharmaceuticald rugs against osteosarcoma.

Synthesis and Antibacterial Activity of Ionic Liquids and Organic Salts Based on Penicillin G and Amoxicillin hydrolysate Derivatives against Resistant Bacteria

“…For the last 12 years, organic salts and ionic liquids (OSILs) from active pharmaceutical ingredients (APIs), or simply API-OSILs [14][15][16][17][18][19][20][21][22], have been studied at the academic level [14,18,19,[23][24][25]. Ionic liquids (ILs) are salts with melting points below 100 • C (some of them are liquid at room temperature) that result from the pairing of organic cations with organic and inorganic anions [14,20,23].…”

Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma

“…The selection of protonated organic superbases (1,1,3,3-tetramethylguanidinium [TMGH] and 1,5-diazabicyclo(4.3.0)non-5-enium [DBNH]) and quaternary ammonium (cholinium [Ch] and 1-(2-hydroxyethyl)-3-methyl-1H-imidazol-3-ium [C 2 OHMIM]) cations relied on the known information about their biocompatibility [15,23]. Despite their low toxicity, the combination of these cations with other APIs has rendered highly active API-OSILs in the past, in particular antimicrobial and anti-tumoral [19,20,22]. The preparation of compounds 1-4 consisted of the addition of the diluted superbases to a dispersion of ALN (pathway A).…”

“…In all cases, the 1 H NMR spectra showed that the cation/anion The preparation of compounds 1-4 consisted of the addition of the diluted superbases to a dispersion of ALN (pathway A). These particular compounds, termed Superionic Liquids of APIs, were prepared according to a previous methodology reported by us for zoledronic acid [22] as well as other APIs [16]. While both monoanionic ALN-OSILs were obtained as solids, the two dianionic were isolated as pastes.…”

“…On the other hand, a combination of ALN with one and two equivalents of [Ch] and [C 2 OHMIM] cations yielded four more ALN-based OSILs (compounds 5-8) by following another methodology already described by our group [15,22]. In this case, quaternary ammonium hydroxide cations are previously prepared by the corresponding halide exchange with hydroxide exchange resins (e.g., Amberlyst A26-OH) in methanolic solution.…”

“…Ionic Liquids (ILs) are defined as salts with a melting point below 100 • C, which display peculiar properties such as negligible vapor pressure, high thermal and chemical stability and tunable physicochemical properties according to the cation-anion combinations. These novel API-OSILs can improve the drug performance in terms of stability, solubility, permeability, biological activity and delivery [10][11][12][13][14][15][16][17][18][19][20][21][22]. Recent achievements showed that the suitable combination between different families of pharmaceutical drugs such as NSAIDs (e.g., ibuprofen and naproxen [15,16]), β-lactam (e.g., ampicillin, amoxicillin, penicillin [16][17][18][19][20]) and fluoroquinolone (ciprofloxacin, norfloxacin [16,21]) antibiotics and bone antiresorptive agents (zoledronic acid [22]) rendered novel pharmaceutical drug formulations based on OSILs.…”