Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3- b ][1,2,4,5]tetrazine derivatives
| Autor: | Zhong-Lu Ke, Feng Xu, Qidong Yan, Wei-ke Lv, Li-qing Zhu, John Wang, Fei-lei Lin, Wei-qiang Yang, Han-gui Wu, Xi Limin, Zhen-Zhen Yang, Hai-Bo Li |
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| Rok vydání: | 2016 |
| Předmět: |
Quantitative structure–activity relationship
Stereochemistry Clinical Biochemistry Triazole Quantitative Structure-Activity Relationship Pharmaceutical Science Antineoplastic Agents Field analysis 010402 general chemistry 01 natural sciences Biochemistry chemistry.chemical_compound Tetrazine Cell Line Tumor Drug Discovery Ic50 values Humans Molecular Biology Homoaromaticity 010405 organic chemistry Organic Chemistry Triazoles In vitro 0104 chemical sciences chemistry Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:4580-4586 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.08.078 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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