Novel hydrazone-isatin derivatives as potential EGFR inhibitors: Synthesis and in vitro pharmacological profiling

被引：19

作者：

Ahmed, Marwa F. ^{[1
,8
]}

El-Haggar, Radwan ^{[2
,9
]}

Almalki, Atiah H. ^{[1
,3
]}

Abdullah, Omeima ^{[4
]}

El Hassab, Mahmoud A. ^{[5
]}

Masurier, Nicolas ^{[6
]}

Hammad, Sherif F. ^{[2
,7
]}

机构：

[1] Taif Univ, Coll Pharm, Dept Pharmaceut Chem, Taif, Saudi Arabia

[2] Helwan Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo, Egypt

[3] Taif Univ, Coll Pharm, Addit & Neurosci Res Unit, Taif, Saudi Arabia

[4] Umm Al Qura Univ, Coll Pharm, Pharmaceut Chem Dept, Mecca, Saudi Arabia

[5] King Salman Int Univ KSIU, Fac Pharm, Dept Med Chem, South Sinai, Egypt

[6] Univ Montpellier, Inst Biomol Max Mousseron IBMM, UMR 5247, CNRS,ENSCM, Montpellier, France

[7] Egypt Japan Univ Sci & Technol E JUST, Basic & Appl Sci Inst, Alexandria, Egypt

[8] Taif Univ, Coll Pharm, Dept Pharmaceut Chem, POB 11099, Taif 21944, Saudi Arabia

[9] Helwan Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11795, Egypt

来源：

ARCHIV DER PHARMAZIE | 2023年 / 356卷 / 09期

关键词：

anticancer; breast cancer; EGFR; hydrazone; isatin; BIOLOGICAL EVALUATION; ANTICANCER ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; DESIGN; ANTITUMOR; ANALOGS; AGENTS; ANTIBACTERIAL; INDIRUBIN; DISCOVERY;

D O I：

10.1002/ardp.202300244

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Merging isatin and arylhydrazone moieties constitutes an efficient strategy to access new potential anticancer derivatives. Consequently, 14 hydrazone-isatin derivatives were synthesized and evaluated for their antiproliferative activity against the NCI-60 cancer cell line panel. A kinase assay demonstrated that compound VIIIb inhibited the epidermal growth factor receptor (EGFR), which was confirmed by docking studies, molecular dynamics, and binding free energy calculations. Further characterizations showed that this compound possesses drug-likeness properties, showed a significant decrease of the cell population in the G2/M phase and led to a significant increase in early and late apoptosis, comparable to erlotinib. Also, VIIIb increased the expression of caspase-3 and Bax and decreased the expression of Bcl-2, confirming its potential as a new proapoptotic compound.

引用

页数：16

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