Synthesis, Characterization, and Examination of Possible Anticancer Effects of a Novel Bis-1,2,3-triazole derivative via Molecular Docking Studies

Abstract

A new bis-1,2,3-triazole compound (6) was synthesized by utilizing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) method and characterized by 1 H, 13 C NMR, and HR-(ESI)-MS analysis. Molecular docking studies against EGFR, mTOR, and p70S6K1 receptor proteins were performed to examine the potential anticancer effects of 6 . The inhibition of these receptors has been considered an important therapeutic strategy in anticancer studies. The docking results were compared with those of anastrozole, which is an anticancer drug, and co-crystallized ligands of EGFR, mTOR, and p70S6K1 receptors, which are FMM for EGFR, P2X for mTOR, and 5FI for p70S6K1. The co-crystallized ligands are highly effective inhibitors for the receptors. According to the docking studies, compound 6 has quite good binding affinities with the three receptors. The best binding energy values with mTOR, p70S6K1, and EGFR of 6 are calculated as -10.38 kcal/mol, -9.93 kcal/mol, and -10.02 kcal/mol, respectively. Conversely, anastrozole’s best binding values are -8.42 kcal/mol, -8.08 kcal/mol, and -7.55 kcal/mol, respectively. On the other hand, when compared to the binding energies of FMM (−13.16 kcal/mol, P2X (−8.81 kcal/mol), and 5FI(−7.6 kcal/mol), it is seen that compound 6 has better binding energy than them, except for FMM. The EIC (Estimated Inhibition Constant) Ki values with mTOR, p70S6K1, and EGFR of 6 are found as 24.81 nM, 52.21 nM, and 45.28 nM, respectively, while anastrozole’s Ki values are 671.53 nM, 1190 nM, and 2950 nM. On the other hand, the Ki values of P2X, 5FI, and FMM are 347 nM, 2700 nM, and 25.5 nM, respectively. These results show that compound 6 has much better binding energy than anastrozole, P2X, and 5FI. Therefore, the compound may show considerable inhibitory effects against these receptor proteins and could be considered a potential candidate drug for anticancer studies.