Efficient synthesis and cytotoxic activity of polysubstituted thieno[2,3-d]pyrimidine derivatives

被引：4

作者：

Wang, Tianshuai ^{[1
,2
,3
]}

Wu, Fengxu ^{[1
,2
,3
]}

Luo, Lun ^{[1
,2
,3
]}

Zhang, Yan ^{[1
,2
,3
]}

Ma, Junkai ^{[1
,2
,3
]}

Hu, Yanggen ^{[1
,2
,3
]}

机构：

[1] Hubei Univ Med, Sch Pharmaceut Sci, Shiyan, Peoples R China

[2] Hubei Univ Med, Hubei Key Lab Wudang Local Chinese Med Res, Shiyan, Peoples R China

[3] Hubei Univ Med, Inst Med Chem, Shiyan, Peoples R China

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2022年 / 1256卷

关键词：

Thieno[2,3-d]pyrimidine; Biological evaluation; Molecular docking; Structure-activity relationship; BIOLOGICAL EVALUATION; MOLECULAR-DYNAMICS; INHIBITORS; DESIGN; THIOPHENE; PROTEIN;

D O I：

10.1016/j.molstruc.2022.132497

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Thienopyrimidine scaffold is a fused heterocyclic ring system that has been found to be an integral part of pharmaceutical products to the improvement of pharmacological and biological activities. A series of polysubstituted thieno[2,3-d]pyrimidine derivatives have been synthesized and tested for their cytotoxic activity against Hela and A549 cancer cell lines in which EGFR is highly expressed. Most of the target compounds 8a-8e showed excellent activity against Hela and A549 cancer cell lines. The most promising compound 8c exhibited the similar IC50 values on A549 cell lines to the lead drug Olmutinib. The molecular docking results indicated that compound 8c bound to EGFR kinase in a different method with Olmutinib. The preliminary structure-activity relationship (SAR) suggested that the introduction of oxygen substituents was more favorable for antitumor activity. Compound 8c proved to be a promising antitumor agent. (C)& nbsp;2022 Elsevier B.V. All rights reserved.

引用

页数：10

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