Discovery of pyrimidine-2,4-diamine analogues as efficiency anticancer drug by targeting GTSE1

doi:10.1016/j.bioorg.2024.107700

科研成果详情

题名	Discovery of pyrimidine-2,4-diamine analogues as efficiency anticancer drug by targeting GTSE1
作者	Xing, Sunhui1; Yang, Huamao1; Chen, Xiaojian 1; Wang, Yan 1; Zhang, Shuyuan1; Wang, Peipei 1; Chen, Chaoyue 1; Wang, Kun 1; Liu, Zhiguo1; Zheng, Xiaohui1,2,3
发表日期	2024-10
发表期刊	Bioorganic Chemistry 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Pyrimidine-2 4-diamine derivatives GTSE1 Anticancer efficacy Cell proliferation Cell migration
其他关键词	CELL-ADHESION ; LUNG-CANCER ; DNA-DAMAGE ; BIOLOGY ; TUMOR ; RADIATION
摘要	A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.
资助项目	National Natural Science Foundation of China [82273995, 82304308, 81973168, 82273788]; National Natural Science Foundation of Zhejiang Province [LY22H310004, LZ22H300002, LQ23B020006]; Wenzhou Basic Medical and Health Technology Project [Y20220190, Y20220195, Y20220200, Y20220202]; Scientific Research Center of Wenzhou Medical university and Wenzhou Key Laboratory of Research and Transformation of Chinese Medicine
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN	0045-2068
EISSN	1090-2120
卷号	151
DOI	10.1016/j.bioorg.2024.107700
页数	17
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS记录号	WOS:001294449800001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39128245
SCOPUSEID	2-s2.0-85200887670
通讯作者地址	[Wang, Kun;Liu, Zhiguo;Zheng, Xiaohui]Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China. ; [Zheng, Xiaohui]Wenzhou Med Univ, Affiliated Hosp 2, Key Lab Pediat Hematol & Oncol Dis Wenzhou, Wenzhou 325027, Zhejiang, Peoples R China. ; [Zheng, Xiaohui]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325035, Zhejiang, Peoples R China.
Scopus学科分类	Biochemistry;Molecular Biology;Drug Discovery;Organic Chemistry
SCOPUS_ID	SCOPUS_ID:85200887670
TOP期刊	TOP期刊
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217474
专题	药学院（分析测试中心）_生物有机与药物化学研究中心附属第二医院第二临床医学院，附属第二医院、育英儿童医院
通讯作者	Wang, Kun; Liu, Zhiguo; Zheng, Xiaohui
作者单位	1.Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 2, Key Lab Pediat Hematol & Oncol Dis Wenzhou, Wenzhou 325027, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325035, Zhejiang, Peoples R China
第一作者单位	药学院（分析测试中心）_生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）_生物有机与药物化学研究中心; 附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院
第一作者的第一单位	药学院（分析测试中心）_生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Xing, Sunhui,Yang, Huamao,Chen, Xiaojian,et al. Discovery of pyrimidine-2,4-diamine analogues as efficiency anticancer drug by targeting GTSE1[J]. Bioorganic Chemistry,2024,151.
APA	Xing, Sunhui., Yang, Huamao., Chen, Xiaojian., Wang, Yan., Zhang, Shuyuan., ... & Zheng, Xiaohui. (2024). Discovery of pyrimidine-2,4-diamine analogues as efficiency anticancer drug by targeting GTSE1. Bioorganic Chemistry, 151.
MLA	Xing, Sunhui,et al."Discovery of pyrimidine-2,4-diamine analogues as efficiency anticancer drug by targeting GTSE1".Bioorganic Chemistry 151(2024).