Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approaches

Triple-negative breast cancer accounts for 10-15% of all breast tumors (TNBC). Triple-negative breast cancer lacks either estrogen or progesterone receptors (ER or PR), producing either too little or too much HER2. (All three tests result in "negative" results for the cells.) These cancers are more common in women under 40 who are Black or have the BRCA1 mutation. TNBC differs from other types of invasive breast cancer in that it has fewer treatment options, a worse prognosis, and grows and spreads more quickly (outcome). So, first of all, the protein of triple-negative breast cancer was collected from the PDB database having the most stable configuration, and a natural bioactive molecule, Scutellarein, was selected. Scutellarein is well-known to possess anti-cancer properties, so its derivatives were chosen to design anticancer drugs through computational tools. In this case, the functional group has applied and modified structural activity relationship methods. Then, the pass prediction score was taken, which indicates the probability of active (Pa) and the probability of inactive (Pi). After that, other in-silco approaches, such as the ADMET parameter, and quantum calculation by Density Functional Theory (DFT), have been conducted. Finally, molecular docking and dynamics have been evaluated against TNBC to determine the binding affinity and stability. Scutellarein derivatives (DM03 at -10.7 kcal/mol, DM04 at -11.0 kcal/mol) have been reported to have a maximum tendency for binding against TNBC. Besides, the molecular dynamic simulation was performed at 100ns and described by root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF), which are much more stable compounds. The pharmacokinetics specifications for a suitable therapeutic candidate were satisfied by these molecules, like as non-carcinogenic, minimal to aquatic and non-aquatic toxicity. Almost all the molecules are highly soluble in the aqueous system. These all-computational data suggested that they might be suitable as a medication for the inhibition of TNBC, and further experimental studies should be carried out.