Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide-hydrazone and carboxamide moiety.
A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50 values of 2.21μg/mL, 1.67μg/mL and 1.11μg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide-hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.
Haifeng
H
He
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.
Xiaoyan
X
Wang
National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
Liqiao
L
Shi
National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
Wenyan
W
Yin
National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China.
Ziwen
Z
Yang
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China. Electronic address: he1208@mail.ccnu.edu.cn.
Hongwu
H
He
National Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Wuhan 430064, China. Electronic address: liangying2004123@163.com.
Ying
Y
Liang
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology*; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006834:Hydrazines; D006835:Hydrazones; D013844:Thiazoles
1,3-Thiazole; Antitumor activity; Apoptosis; Carboxamide; Hydrazide–hydrazone