title: How to increase the safety and efficacy of compounds against neurodegeneration? A multifunctional approach.
abstract: Successful drug design requires not only the detailed knowledge of the pharmacokinetic and pharmacodynamic profiles of the drug candidate portfolio but also a thorough documentation of the possible toxic effects on humans and the environment. Thus, experimental and computational strategies  able to measure or predict specific profiles of designed compounds related to their potential toxicity are highly desired. Moreover, a strategy to avoid toxic effects thus enhancing the potential efficacy of drug candidates is of great interest. To fulfil this aim, the pharmacochemistry research  unit at the EPGL has recently developed and improved methodologies that detect the potential human health and environmental hazards of compounds active against neurodegeneration at an early stage. A three-step strategy is presented herein. In particular, i) an alternative index to model the  bioconcentration of chemicals in the environment was determined; ii) the antioxidant activity of chemical species against free radicals was evaluated. Moreover, since antioxidants play a key role in both toxicity prevention and neuroprotection, iii) the potential interaction of such compounds  with enzymatic targets involved in the neurodegenerative cascade was investigated in silico.
authors.affiliation: School of Pharmaceutical Sciences University of Geneva, University of Lausanne Pharmacochemistry Quai Ernest-Ansermet 30 CH-1211 Geneva 4, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.forename: Claudia
authors.initials: C
authors.lastname: Simoes-Pires
authors.forename: Sophie
authors.initials: S
authors.lastname: Martel
authors.forename: Delphine
authors.initials: D
authors.lastname: Cressend
authors.forename: Amandine
authors.initials: A
authors.lastname: Guillot
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
mesh_terms: D000465:Algorithms; D000975:Antioxidants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004787:Environmental Pollution; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents