title: Development of an in Silico Profiler for Mitochondrial Toxicity.
abstract: This study outlines the analysis of mitochondrial toxicity for a variety of pharmaceutical drugs extracted from Zhang et al. ((2009) Toxicol. In Vitro, 23, 134-140). These chemicals were grouped into categories based upon structural similarity. Subsequently, mechanistic analysis was undertaken for each category to identify the molecular initiating event driving mitochondrial toxicity. The mechanistic information elucidated during the analysis enabled mechanism-based structural alerts to be developed and combined together to form an in silico profiler. This profiler is envisaged to be used to develop chemical categories based upon similar mechanisms as part of the adverse outcome pathway paradigm. Additionally, the profiler could be utilized in screening large data sets in order to identify chemicals with the potential to induce mitochondrial toxicity.
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Byrom Street, Liverpool L3 3AF, United Kingdom.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Nelms
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Byrom Street, Liverpool L3 3AF, United Kingdom.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Mellor
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Byrom Street, Liverpool L3 3AF, United Kingdom.
authors.forename: Mark T D
authors.initials: MT
authors.lastname: Cronin
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Byrom Street, Liverpool L3 3AF, United Kingdom.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Madden
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Byrom Street, Liverpool L3 3AF, United Kingdom.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Enoch
mesh_terms: D000777:Anesthetics / Q000737:chemistry / Q000633:toxicity; D000890:Anti-Infective Agents / Q000737:chemistry / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000633:toxicity; D001647:Bile Acids and Salts / Q000737:chemistry / Q000633:toxicity; D062126:Databases, Chemical; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D000777:Anesthetics; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001647:Bile Acids and Salts; D007004:Hypoglycemic Agents; D018377:Neurotransmitter Agents