Novel sulfonyl thiazolyl-hydrazone derivatives as EGFR inhibitors: Design, synthesis, biological evaluation and molecular docking studies.
Thoraya A Farghaly, Eman M H Abbas, Amerah M Al-Soliemy, Rehab Sabour, Mohamed R Shaaban
Author Information
Thoraya A Farghaly: Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. Electronic address: thoraya-f@cu.edu.eg.
Eman M H Abbas: Department of Chemistry, Natural and Microbial Products, National Research Center, Dokki, Cairo, Egypt.
Amerah M Al-Soliemy: Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, Saudi Arabia.
Rehab Sabour: Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Mohamed R Shaaban: Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, Saudi Arabia. Electronic address: rabiemohamed@hotmail.com.
New hydrazonoyl-sulfonylthiazoles were designed and synthesized as EGFR inhibitors. The new sulfonylthiazole derivatives were assessed in vitro to measure their effect on EGFR. They revealed marked inhibitory activity against EGFR kinase having IC range from 0.037 to 0.317 μM compared to reference drug dasatinib (IC = 0.077 μM). Six derivatives of the newly synthesized compounds showed potent inhibitory activity relative to dasatinib. Furthermore, the new hits were examined concerning their cytotoxic effect on human breast cancer cell line (MCF7), hepatic cancer cell line (HepG2) using MTT assay. N-(2-Benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-thiazol-2-yl)-hydrazine (IC = 1.24 μM) revealed higher potency than dasatinib (IC = 11.6 μM) against MCF7cell line. Besides, N-(2-benzenesulfonyl-1-phenyl-ethylidene)-N'-(4-methyl-5-p-tolylazo-thiazol-2-yl)-hydrazine exhibited excellent cytotoxicity against HepG2cell line (IC = 3.61 μM), exceeding that of dasatinib (IC = 14.10 μM). In addition to low cytotoxic effect on normal (WI-38) cells, describing the high safety profiles of these compounds. Moreover, molecular docking was done in order to determine the possible binding modes of such compounds inside the binding site of EGFR.
