43.47 to – 21.61 kcal/mol while erlotinib, an approved drug, showed interaction at – 45.49 kcal/mol. Eight vinyl sulfones were chosen using the interaction energy lower than – 37.5 kcal/mol. These compounds can interact with important surrounding residues in ATP-binding pocket of EGFR-TK via H-bonding, pi interactions and van der Waals (vdW) forces. Physical properties of the eight vinyl sulfones were investigated in term of the druglikeness by considering their physicochemical properties. The obtained results revealed that all vinyl sulfones showed acceptable values. Therefore, these VFs could likely be developed as promising novel EGFR-TK inhibitors. Next, EGFR-TK inhibitory activity of eight vinyl sulfones and erlotinib was evaluated using ADP-Glo kinase
assay. There was a vinyl sulfone (VF16) that showed the highest EGFR-TK inhibitory activity (98.91%), which was higher than erlotinib (87.80%) with the half-maximal inhibitory concentration (IC50) values against EGFR-TK at 7.85 0.88 nM (VF16) and 26.09 5.42 nM (erlotinib). VF16 also exhibited potent anti-lung cancer activity against three lung cancer cell lines (A459, A431 and H1975 cell lines). In conclusion, this work combined the computational and experiment techniques to identify new EGFR inhibitor based on vinyl sulfone derivatives. The results indicated that VF16 could be developed as a promising new anti-cancer drug targeting EGFR-TK
Thitinan Aiebchun, Panupong Mahalapbutr, Atima Auepattanapong, Onnicha Khaikate, Supaphorn Seetaha, Lueacha Tabtimmai, Chutima Kuhakarn, Kiattawee Choowongkomon* and Thanyada Rungrotmongkol* “Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies” Molecules 2021, 26, 2211.