Exploring Cheminformatic Toolsets for Predicting the Dermal Toxicity of Furanocoumarins

Douglas Vieira Thomaz, Matheus Gabriel de Oliveira, Vinicius Barreto da Silva, Pierre Alexandre dos Santos, Rene Oliveira do Couto, Rene Oliveira do Couto


Linear furanocoumarins are skin sensitizers and anticancer agents whose appeal in skincare therapeutics is widely exploited. Owing to the need to predict the biological activities of medicines, this work aimed the investigate the predicted dermal toxicity of linear furanocoumarins through chemoinformatic approaches. Therefore, eight major linear furanocoumarins of interest in medicine were selected, and their pharmacophores / toxicophores were modelled and inputted in several databases and cheminformatic toolsets previously described in the literature. Moreover, Principal Components Analysis was performed to allow multivariable comparisons. Results showcased that the first two PCs accounted for 95.48% of all variance in the model, and molecular weight and polar surface showcased a positive correlation to Log P and Log Kp, which may be involved in skin penetration. Moreover, the pharmacophore modelling evidenced superimposition between linear furanocoumarins, ethidium bromide and acridine orange, thereby suggesting that these compounds share similar biological effects, supported by their acknowledged DNA intercalating activities. Therefore, this work showcased the application of various cheminformatic tools to screen the dermal toxicity of chemicals.


skin sensitizer; DNA intercalation; secondary metabolite; in silico; molecular modelling


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