Predictive Analysis of the Pharmacokinetic and Toxicological Endpoints of Naphthalene and its Derivatives

Abstract

The study was conducted to determine the putative pharmacokinetic and toxicological properties of naphthalene and its derivatives, hence determining their harmful effects, if any in the normal daily function of the human system. The effects of these compounds on hormonal homeostasis and the endocrine system were also evaluated. The pharmacokinetic ADMET (Absorption, distribution, metabolism, excretion, and toxicity) properties were determined by running a computer-simulated prediction on the compounds based on their canonical SMILES (Simplified Molecular Input Line Entry System) structure using the pkCSM online prediction tool. The Canonical SMILES structures were obtained from the PubChem database. The predictive endocrine disruption potential was evaluated using the Endocrine Predictome computational tool which uses a molecular docking system to predict the interaction between the investigated chemicals and the affected nuclear receptors. The results showed that naphthalene and the derivatives have relatively high log P values, implying their respective lipophilicity; however, only naphthalene-1,2,6,7-tetrol could not permeate the blood-brain barrier. Moreover, all the selected compounds are substrates of the P-glycoprotein and do not inhibit their activity. The results also indicated that naphthalene and all four selected derivatives could have an inhibitory effect on the CYP1A2 enzyme and a disruptive effect on some endocrine functions due to their respective high binding affinity with endocrine receptors. In conclusion, the study showed that naphthalene and the derivatives could have adverse effects on the physiological function of the body vis-à-vis neurological damages, and various metabolic disorders. The predictive influence on the endocrine system also indicated the selected chemicals could induce detrimental changes in endocrine functions.