Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies
Thitinan Aiebchun,
Panupong Mahalapbutr,
Atima Auepattanapong,
Onnicha Khaikate,
Supaphorn Seetaha,
Lueacha Tabtimmai,
Chutima Kuhakarn,
Kiattawee Choowongkomon,
Thanyada Rungrotmongkol
Affiliations
Thitinan Aiebchun
Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Panupong Mahalapbutr
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Atima Auepattanapong
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Bangkok 10700, Thailand
Onnicha Khaikate
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Bangkok 10700, Thailand
Supaphorn Seetaha
Department of Biochemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand
Lueacha Tabtimmai
Department of Biotechnology, Faculty of Applied Science, King Mongkut’s University of Technology of North Bangkok, Bangkok 10800, Thailand
Chutima Kuhakarn
Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Bangkok 10700, Thailand
Kiattawee Choowongkomon
Department of Biochemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand
Thanyada Rungrotmongkol
Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC50 value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC50 values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.