Antimicrobial activity on phytopathogenic bacteria and yeast, cytotoxicity and solubilizing capacity of deep eutectic solvents

3 Figuras.-- 4 TablasThe toxicity on oenological yeasts and plant pathogens of eight deep eutectic solvents (DESs) composed of ChCl:Sucrose (1:2), ChCl:1,4-butanediol (1:5), ChCl:Xylitol (2:1), ChCl:1,2-propanediol (1:1), Fructose:Glucose:Sucrose (1:1:1), Betaine:Sucrose (2:1), Betaine:Sucrose (4:1) and Fructose-Glucose-Sucrose (2:3.6:1) was evaluated and compared with the classic solvents dimethylsulfoxide (DMSO), ethanol and glycerol. Most yeast and bacteria were tolerant to DESs consisting of three sugars in a concentration range of 75–600 x 103mg/L for yeasts and 75–1200 x 103mg/L for bacteria. These DESs showed less toxicity than glycerol or DMSO for most microorganisms. The effect of six DESs, ChCl:Sucrose (1:2), ChCl:Xylitol (2:1), Fructose:Glucose:Sucrose (1:1:1), Betaine:Sucrose (2:1), Betaine:Sucrose (4:1) and Fructose-Glucose-Sucrose (2:3.6:1) in different human cancer cell lines (Caco-2, HeLa and HepG2 cells), as well as in peripheral blood mononuclear cells (PBMCs) from healthy volunteers, was studied using flow cytometry. As a result, DESs at concentrations below 1%, affected tumor cells; however, healthy PBMCs were unaffected. In addition, the solubility of poorly-soluble subtances in water (quercetin, phenylmethylsulfonyl fluoride (PFMS), camptothecin (CPT), oleanolic acid, palmitic acid and Red O oil) was evaluated in all DESs previously tested plus two organic acidbased DESs, Betaine:Levulinic acid (1:2) and ChCl:Glycolic acid:Oxalic acid (1:1.6:0.4). All they were compared with conventional solvents (water, DMSO or ethanol) to determine their efficacy as drug solvents. As a result, DESs solubilized quercetin and CPT in the same range as conventional solvents. The antioxidant properties of quercetin solubilized in two DESs and in DMSO were studied in Caco-2 cells. A solution of tert-butyl hydroperoxide (TBH) was used as an inducer of intracellular reactive oxygen species (ROS), resulting in that quercetin's ability to reduce ROS production did not differ when it was solubilized in DESs or DMSO. In this study, we determined the low toxicity of the DESs analyzed on oenological yeasts, phytopathogenic microorganisms and on healthy human cells. The toxicity of DESs on cancer cell lines was also showed. In addition, the ability of DESs to dissolve poorly water-soluble compounds or other substances of interest was also demonstrated, suggesting their use as safe solvents or cryoprotectors useful at an industrial level.This work was supported by the Spanish Government (AGL2016-79088-R and AGL2016-80852-R) and by the Spanish FPI funding program (MEIC) (BES-2017–079648). Sergio Lopez thanks the ‘V Own Research Plan’ of the University of Seville (VPPI‐US) contract (co-founded by the European Social Fund).Peer reviewe