title: Establishment of an in silico phototoxicity prediction method by combining descriptors related to photo-absorption and photo-reaction.
abstract: One of the mechanisms of phototoxicity is photo-reaction, such as reactive oxygen species (ROS) generation following photo-absorption. We focused on ROS generation and photo-absorption as key-steps, because these key-steps are able to be described by photochemical properties, and these properties are dependent on chemical structure. Photo-reactivity of a compound is described by HOMO-LUMO Gap (HLG), generally. Herein, we showed that HLG can be used as a descriptor of the generation of reactive oxygen species. Moreover, the maximum-conjugated π electron number (PENMC), which we found as a descriptor of photo-absorption, could also predict in vitro phototoxicity. Each descriptor could predict in vitro phototoxicity with 70.0% concordance, but there was un-predicted area found (gray zone). Interestingly, some compounds in each gray zone were not common, indicating that the combination of two descriptors could improve prediction potential. We reset the cut-off lines to define positive zone, negative zone and gray zone for each descriptor. Thereby we overlapped HLG and PENMC in a graph, and divided the total area to nine zones with cut-off lines of each descriptor. The rules to prediction were decided to achieve the best concordance, and the concordances were improved up to 82.8% for self-validation, 81.6% for cross-validation. We found common properties among false positive or negative compounds, photo-reactive structure and photo-allergenic, respectively. In addition, our method could be adapted to compounds rich in structural diversity using only chemical structure without any statistical analysis and complicated calculation.
authors: Senju Pharmaceutical Co. Ltd., Toxicology Research Laboratory.
authors: Yu
authors: Y
authors: Haranosono
authors: Masaaki
authors: M
authors: Kurata
authors: Hideyuki
authors: H
authors: Sakaki
mesh_terms: D017484:Dermatitis, Phototoxic / Q000175:diagnosis* / Q000209:etiology* / Q000378:metabolism; D010083:Oxidants, Photochemical / Q000378:metabolism; D055668:Photochemical Processes; D011237:Predictive Value of Tests; D017382:Reactive Oxygen Species / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D010083:Oxidants, Photochemical; D017382:Reactive Oxygen Species