A Bifunctional Dimethylsulfoxide Substitute Enhances the Aqueous Solubility of Small Organic Molecules

Abstract

An oxetane-substituted sulfoxide has demonstrated potential as a dimethylsulfoxide substitute for enhancing the dissolution of organic compounds with poor aqueous solubilities. This sulfoxide may find utility in applications of library storage and biological assays. For the model compounds studied, significant solubility enhancements were observed using the sulfoxide as a cosolvent in aqueous media. Brine shrimp, breast cancer (MDA-MB-231), and liver cell line (HepG2) toxicity data for the new additive are also presented, in addition to comparative IC 50 values for a series of PKD1 inhibitors.

Synthesis and Evaluation of Potent KCNQ2/3-Specific Channel Activators

“…Moreover, we introduced a preliminary series of heterocycle analogs of the phenyl group in zone 1, that is, a more electron-rich thiophene (NR579_46) and a more electron-deficient thiazole (NR579_38). Finally, our class III design modified the steric size of the ethylcarbamate in zone 3 by introducing an iso-propyl group (NR561_62) and the solubilizing oxetane derivatives NR579_45 and NR579_36 (Sprachman and Wipf, 2012;Skoda et al, 2014). For synthesis details, full chemical names, and spectroscopic information on these compounds, see the Supplemental Data.…”

Evaluation of potential ionizing irradiation protectors and mitigators using clonogenic survival of human umbilical cord blood hematopoietic progenitor cells

“…The water-soluble bifunctional dimethylsulfoxide analog, MMS-350, which can also be used as a vehicle for administration of other drugs [11] demonstrated protective and mitigative properties as a single agent in mouse cells in total body irradiated mice, and was effective with the CB MNC assay. The mechanism of action of MMS-350 is currently being studied, but is hypothesized to function as an antioxidant scavenger of ROS based on prior data with DMSO [28].…”

“…The drugs GS-nitroxides (JP4-039 and XJB-5-131) [1, 3], bifunctional sulfoxide (MMS-350) [11], PI3K inhibitor (LY294002) [14], and the triphenylphosphonium mitochondrial targeted imidazole fatty acid (TPP-IOA) [16] have been described. JP4-039, XJB-5-131, MMS-350 [11], BEB55 and MCF-201-89 [3] were synthesized according to published protocols and used after passing Quality Control by Liquid Chromatography/Mass Spectroscopy Standards (purity >92%) [16].…”

“…JP4-039, XJB-5-131, MMS-350 [11], BEB55 and MCF-201-89 [3] were synthesized according to published protocols and used after passing Quality Control by Liquid Chromatography/Mass Spectroscopy Standards (purity >92%) [16]. TPP-OFA [13] was synthesized by Dr. Jeffrey Atkinson (Brock University, St Catharines, Ontario, Canada), LY294002 (Enzo Life Sciences, Farmingdale NY), methoxamine, isoproterenol,propranolol and glyburide (Sigma, St. Louis, MO) were purchased.…”

“…XJB-5-131, another mitochondrial targeted GS-nitroxide, was shown to be a radioprotector [5] and neuroprotector [10]. MMS-350 is a novel water-soluble sulfoxide developed as a 2 nd generation, selective analog of dimethyl sulfoxide (DMSO) [10], a known radioprotector in mice [11]. A mitochondria-targeted inhibitor of irradiation-induced peroxidase activity of cytochrome c/cardiolipin complexes, triphenylphosphonium imidazole fatty acid (TPP-IOA) has been shown to mitigate radiationinduced cell death in mouse cells [12–13], and the phosphoinositol-3 kinase (PI3K) inhibitor LY294002 has been shown to mitigate radiation-induced apoptosis in mouse cells in vitro [14].…”