Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API-ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API-ILs showed IC50 values between 5 and 42 nM, activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines-skin (SF) and gingival fibroblasts (GF)-indicates that the majority of these API-ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1-hydroxyethyl-3-methylimidazolium-ampicillin pair ([C2 OHMIM][Amp]), making this the most suitable lead API-IL for future studies.

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 Escherichia coli and Staphylococcus aureus 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.

Herein we report the synthesis of novel ionic liquids( ILs) and organic salts by combining ibuprofen as anion with ammonium, imidazolium, or pyridinium cations. The methodology consists of an acid-base reactiono fn eutral ibuprofen with cation hydroxides, which were previouslyp repared by anion exchange from the correspondingh alide salts with Amberlyst A-26(OH). In comparison with the parent drug, these organic salts display higher solubility in water and biological fluids and as maller degree of polymorphism, which in some cases was completely eliminated. With the exceptiono f [ C 16 Pyr][Ibu] and [N 1,1,2,2OH1 ][Ibu],t he prepared salts did not affect the viabilityo f normalh uman dermalf ibroblasts or ovarian carcinoma (A2780) cells. Therefore, these ibuprofen-based ionic liquids may be very promising lead candidates for the development of effective formulationso ft his drug.Ibuprofen is used in the treatmento fp aina nd inflammation in rheumatoid arthritisa nd other musculoskeletal disorders in both humans and animals. [1] It is considered one of the Essential Medicines by the World Health Organization( WHO). Ibuprofen is an onsteroidal anti-inflammatory drug (NSAID), which nonselectively inhibits cyclooxygenases 1a nd 2( COX-1a nd COX-2), resulting in the inhibition of prostaglandins. [2] Althoughi th as as trongera nalgesice ffect than other NSAIDs in some types of pain, [3] the mean onset of action per 400 mg dose is 45 minutes, which can be critical in an acute painsituation, where rapid relief is critical. [4] Its low solubility in the acidic aqueous media of the stomach is responsible for ibuprofen'ss low pharmaceutical effect, [5] despite its ease of permeability through the gastrointestinal membranes, rendering close to 100 %b ioavailability. [6] To increase the absorption rate and to provide faster pain relief, new formulations of ibuprofen have been developed over the years, particularly salts (sodium, [7] lysine, [8] and arginine [9] )a nd extrudate. [10] These forms, however,d on ot tackle the degree of ibuprofen's poly-morphism, [11] whose different crystal shapes display distinct pharmaceutical effects.For the last 10 years, ionic liquids (ILs) from active pharmaceuticali ngredients (APIs), or simply API-ILs, have been studied at the academic level, as the third generation of ILs. [12][13][14][15] ILs are salts with meltingt emperatures below 100 8C, with some of them being liquid at room temperature (RTILs), that result from the combinationoforganic cations with organic and inorganic anions. The scope of their physicala nd chemical properties has promptedt he study and application of these compounds in several areas of science and technology. [16] In the field of pharmaceutical sciences,w ea nd others have reported that the cation-anion interactions in the prepared API-ILs induce improved physicochemical properties over the original drugs, decrease toxicityt oward healthyc ells, and thus render potentially enhanced pharmaceutical activity to the API. [17][18][19][20][21][22] In more detail,s u...