In Silico ADME Prediction and Molecular Docking of 1,2,3-Triazole-based Compounds Against Human Aromatase Cytochrome P450

Abstract

Objective: Inhibition of the human aromatase cytochrome P450 enzyme has been emphasized as being an efficient mechanism for reducing high estrogen levels in the treatment of breast cancer. Methods: Molecular docking and in silico ADME predictions were performed for a set of 1,2,3-triazole-based compounds aiming for the discovery of new therapeutics targeting the human aromatase cytochrome P450 enzyme. Results: The results showed that compounds 1-3 are capable of binding to the enzyme active site, while compounds 4-8 and 9-11 are capable of binding to the potential allosteric sites 1 and 2 of the enzyme, respectively. Furthermore, all compounds 1-7 and 9-11 were predicted to be orally bioavailable, and compounds 1-3 , 9 , and 11 were anticipated to be blood-brain barrier permeants. Conclusion: Most of the designed compounds possessed relatively good binding affinities to the human placental aromatase cytochrome P450 enzyme and promising in silico ADME-related properties for further optimization towards developing novel human aromatase inhibitors.