Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives.
A series of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives have been synthesized and their structures were confirmed by single-crystal X-ray diffraction. Compared to some reported structures of 1,6-dihydro-1,2,4,5-tetrazine, these compounds can't be considered as having homoaromaticity. Their antiproliferative activities were evaluated against MCF-7, Bewo and HL-60 cells in vitro. Two compounds were highly effective against MCF-7, Bewo and HL-60 cells with IC50 values in 0.63-13.12μM. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 51 [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine derivatives with antiproliferative activity against MCF-7 cell. Models with good predictive abilities were generated with the cross validated q(2) values for CoMFA and CoMSIA being 0.716 and 0.723, respectively. Conventional r(2) values were 0.985 and 0.976, respectively. The results provide the tool for guiding the design and synthesis of novel and more potent tetrazine derivatives.
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China. Electronic address: xufeng901@126.com.
Feng
F
Xu
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Zhen-Zhen
ZZ
Yang
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Zhong-Lu
ZL
Ke
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Li-Min
LM
Xi
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Qi-Dong
QD
Yan
Zhe Jiang Hisoar Pharmaceutical Co. LTDTaizhou 318000, PR China.
Wei-Qiang
WQ
Yang
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Li-Qing
LQ
Zhu
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Fei-Lei
FL
Lin
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Wei-Ke
WK
Lv
Chemical Pharmaceutical Research Institute, Taizhou Vocational & Technical College, Taizhou 318000, PR China.
Han-Gui
HG
Wu
ImmuOn Therapeutics, Chenqiao BridgePark, Nantong 226003, PR China.
John
J
Wang
Department of Clinical Laboratory Medicine, Nantong Maternity and Child Health Hospital, Nantong 226018, PR China.
Hai-Bo
HB
Li
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D021281:Quantitative Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014230:Triazoles
3D-QSAR; Antiproliferative activity; CoMFA; CoMSIA; Tetrazine; Triazole; X-ray diffraction