Synthesis, cytotoxicity and molecular docking of novel quinazoline-4 (3H)-thione derivatives as EGFR-TKIs

被引：0

作者：

Halim, Alyaa S. Abdel ^{[1
]}

Salem, Marwa S. ^{[2
]}

Al-Mabrook, Selima A. M. ^{[2
,3
]}

El-Hashash, Maher A. E. M. ^{[2
]}

机构：

[1] Ain Shams Univ, Fac Sci, Biochem Dept, Cairo 11566, Egypt

[2] Ain Shams Univ, Fac Sci, Chem Dept, Cairo, Egypt

[3] Alasmarya Islamic Univ, Fac Sci, Chem Dept, Zliten, Libya

来源：

JOURNAL OF THE INDIAN CHEMICAL SOCIETY | 2024年 / 101卷 / 11期

关键词：

Anti-proliferative potency; EGFR; Molecular docking; Quinazoline-4(3H)-Thione; Tyrosine kinase inhibitors; INHIBITORS; GROWTH;

D O I：

10.1016/j.jics.2024.101388

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Quinazoline nucleus is a distinct scaffold with fascinating pharmacological characteristics. New quinazoline-4 (3H)-thiones were synthesized and evaluated for their cytotoxic properties against two human cancer cell lines. Molecular investigations on their mechanism of action were conducted. The most potent derivatives were examined by molecular docking as EGFR-TKIs, and their ADME properties were predicted using the SwissADME tool. Derivatives 4, 10, and 12 exhibited the most notable cytotoxicity, as evidenced by their ability to upregulate p53 and caspase-3 expression while downregulating CDK1, inhibiting EGFR activity and downregulating EGFR and ERK1/2 signaling. These derivatives docked well with EGFR and had promising drug-like properties. Our derivatives deserve further optimization not only as novel anticancer agents but also as potent EGFR-TKIs.

引用

页数：15