DOI: 10.1002/vjch.202200135 ISSN: 2572-8288

In silico screening of alkaloids as potential inhibitors of HER2 protein for breast cancer treatment

Bui Thanh Tung, Nguyen Nhu Son, Nguyen Bao Kim, Do Thi Hong Khanh, Phan Hong Minh
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In breast cancers, the expression of the human epidermal growth factor‐2 (HER2) receptor protein target is overexpressed, which plays a critical role in the development of breast cancer. The HER2 inhibitor neratinib, which is currently on the market, specifically targets the ATP‐binding site of the receptors in the EGFR family to inhibits phosphorylation and several HER downstream signaling pathways but it has adverse effects. Phytochemicals provide a useful substitute because they have less adverse effects and are reasonably priced. Hence, this study focused on finding alkaloid compounds collected from Chemfaces database that inhibit HER2 enzyme employing computational methods such as molecular docking and ADMET prediction. Out of 118 phytochemicals docked to the ATP binding site of the HER2 kinase domain, 10 alkaloid compounds (coptisine, sanguinarine, sorafenib, abiraterone acetate, nocamycin I, tirandamycin B, mahanine, tomatidine, cyclopamine and irinotecan hydrochloride) exhibited higher binding affinity than the reference inhibitor and satisfied the Lipinski's rule of five. All compounds have good pharmacokinetic properties. Therefore, these ten compounds could be potential bioactive molecules to act as inhibitor of HER2 protein. To fully assess the potentials of these phytochemicals, experimental investigations will be required. Our study may accelerate the development of HER2 inhibitor drug.

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