title: Natural deep eutectic solvents: cytotoxic profile.
abstract: The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures.
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, 50603 Kuala Lumpur, Malaysia ; Department of Civil Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Maan
authors.identifier: 0000-0002-2179-0801
authors.initials: M
authors.lastname: Hayyan
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, 50603 Kuala Lumpur, Malaysia ; Department of Chemical Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Yves Paul
authors.initials: YP
authors.lastname: Mbous
authors.affiliation: Department of Pharmacology, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chung Yeng
authors.initials: CY
authors.lastname: Looi
authors.affiliation: Department of Medical Microbiology, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Won Fen
authors.initials: WF
authors.lastname: Wong
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, 50603 Kuala Lumpur, Malaysia ; Institute of Halal Research University of Malaya (IHRUM), Academy of Islamic Studies, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Adeeb
authors.initials: A
authors.lastname: Hayyan
authors.affiliation: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, 50603 Kuala Lumpur, Malaysia ; Department of Chemical Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Zulhaziman
authors.initials: Z
authors.lastname: Salleh
authors.affiliation: UiTM Medical Specialist Centre, University of Technology MARA, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Ozair
authors.initials: O
authors.lastname: Mohd-Ali
keywords: COSMO-RS; Cancer cell line; Choline chloride; Cytotoxicity; Green solvents; Ionic liquids; Natural deep eutectic solvents