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Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma

Publication . Teixeira, Sónia; Santos, Miguel M.; Fernandes, Maria H.; Costa-Rodrigues, Joao; Branco, Luís C.

Herein the quantitative synthesis of eight new mono- and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.

2020Journal article

Open access

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

Publication . Ferraz, Ricardo; Silva, Dário; Dias, Ana Rita; Dias, Vitorino; Santos, Miguel M.; Pinheiro, Luís; Prudêncio, Cristina; Noronha, João Paulo; Petrovski, Željko; Branco, Luís C.

The preparation and characterization of ionic liquids and organic salts (OSILs) that contain anionic penicillin G [secoPen] and amoxicillin [seco-Amx] hydrolysate derivatives and their in vitro antibacterial activity against sensitive and resistant Escherichiacoli and Staphylococcusaureus strains is reported. Eleven hydrolyzed β-lactam-OSILs were obtained after precipitation in moderate-to-high yields via the neutralization of the basic ammonia buffer of antibiotics with different cation hydroxide salts. The obtained minimum inhibitory concentration (MIC) data of the prepared compounds showed a relative decrease of the inhibitory concentrations (RDIC) in the order of 100 in the case of [C2OHMIM][seco-Pen] against sensitive S. aureus ATCC25923 and, most strikingly, higher than 1000 with [C16Pyr][seco-Amx] against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. These outstanding in vitro results showcase that a straightforward transformation of standard antibiotics into hydrolyzed organic salts can dramatically change the pharmaceutical activity of a drug, including giving rise to potent formulations of antibiotics against deadly bacteria strains.

2020Journal article

Open access

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

Publication . Teixeira, Sónia; Santos, Miguel M.; Ferraz, Ricardo; Prudêncio, Cristina; Fernandes, Maria H.; Costa-Rodrigues, Joao; Branco, Luís C.

Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium 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. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C3 OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.

2019Journal article

Open access