In Silico study of the effect of substituents on the structure of N-benzoyl-N’-naphthylthiourea as anti-breast cancer HER-2 positive candidates

One of the critical strategies in developing new drugs is to design drugs through structural modification. The structural modification leads to changes in the structure of a compound, thereby changing the compound’’s physicochemical properties, including lipophilic, electronic, and steric properties. These changes will cause changes in the biological activity of the compound. This study aimed to determine the effect of substituents on the benzoyl group of the compound N-benzoyl-N’-naphthylthiourea (BNTU) on the anti-breast cancer activity of HER-2 in silico. Molecular docking of BNTU lead compound and derivatives using Autodock tools software against HER-2 receptors (PDB ID: 3RCD). Compared to lipophilic and steric properties, electronic properties influence the anti-breast cancer activity of HER-2 on BNTU-derived compounds. The binding score (∆G) of BNTU-derived compounds with strong electronic substituents was more negative than lipophilic and steric substituents. However, there is an anomaly in BNTU derivatives with fluoro (F) substituents because they have the lowest anticancer activity compared to the other BNTU derivatives. Anti-breast cancer activity of BNTU-derived compounds is influenced by variations in substituents, especially by the electronic properties (electron withdrawing groups) of these substituents. Compounds with Br substituents have a better affinity for HER-2 receptors than the lead compound BNTU and other BNTU derivatives.