Thymoquinone and its derivatives against breast cancer with HER2 positive: in silico studies of ADMET, docking and QSPR

Abstract

Abstract Objectives The high prevalence of HER2-positive breast cancer has become a significant concern in the health sector. The problem is more complex with the side effects of breast cancer drugs currently used. Thymoquinone (TQ), the main bioactive compound in Nigella sativa, has been shown to have anticancer activity. However, it is necessary to modify the structure of the thymoquinone derivatives to improve drug bioavailability. This study uses an in silico approach to predict pharmacokinetic profile, docking, quantitative structure–properties relationship (QSPR) of new thymoquinone-derived compounds as candidates cytotoxic agent for breast cancer with HER-2 positive. Methods The prediction of ADMET was using pkCSM online. Molecular docking was used to determine thymoquinone derivatives activity using Molegro Virtual Docker version 5.5 by docking the thymoquinone derivatives to the HER2 receptor targets, PDB ID 3PP0 and QSPR analysis using the IBM SPSS 21 version. Results The 35 thymoquinone derivatives showed good physicochemical and absorption properties and not hepatotoxic, so they are suitable for oral drugs. The molecular docking of 35 thymoquinone derivatives against 3PP0 proteins showed better activity than thymoquinone. One of the thymoquinone derivatives, TQ 15, showed the largest negative RS value, meaning that is predicted to have the highest anticancer activity. Based on the QSPR analysis, the essential parameter in determining 35 thymoquinone derivatives activity was the lipophilic and steric parameter. Conclusions Based on in silico test, thymoquinone derivative, TQ 15, had the potential to be further developed as a HER2-positive breast cancer drug.