Design and synthesis of new anticancer scaffolds; pyrazolo[3,4-d][1,2,3]triazine derivatives, is a promising solution to overcome drug resistance problem. A series of (E)-2-cyano-N-(aryl)-3-methylthio-3-(substituted-amino)acrylamides 3a-e was synthesized and transformed to the 3-aminopyrazole derivatives 4a-e which were then transformed to the target pyrazolotriazinones 6a-e. All compounds were evaluated for their anticancer activity against three different cancer cell lines namely Huh-7, Panc-1 and CCRF. Compounds 3a, 3c, 6a and 6c showed excellent anticancer activity against Huh-7 cell line (IC: 4.93-8.84 μM vs doxorubicin 5.43 μM). Similarly, compounds 6a and 6d showed excellent activities against Panc-1 cells (IC: 9.91 μM and 4.93 μM vs doxorubicin 6.90 μM). Caspase-Glo 3/7 assay was done and the results revealed that the pro-apoptotic activity of the target compounds could be due to the stimulation of caspases 3/7. Microarray experiment for Huh-7 cells treated with 6c was performed to search for other molecular changes. SLC26A3, UGT1A1, UGT2B15, UGT2B7, DNASE1, MUCDH1 and UGT2B17 were among the up-regulated genes, while, GIP3, TAGL, THBS1, IFI27, FSCN1 and SOCS2 were among the most extensively down-regulated genes. These genes belong to apoptosis, metabolism, cell cycle, tumor growth and suppressor genes. Finally, pyrazolo[3,4-d][1,2,3]triazine derivatives could be potent anticancer drugs in the future.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2017.10.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis of 4-Amino-5-nitro-7-pyrazolo[3,4-][1,2,3]triazine-2-oxide and Its Heat-Resistant Derivatives.
Org Lett
November 2024
School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
4-Amino-5-nitro-7-pyrazolo[3,4-][1,2,3]triazine-2-oxide () is synthesized via one step in this study. Subsequently, 4,7-diamino-5-nitro-pyrazolo[3,4-][1,2,3]triazine-2-oxide (), 4-oxo-5-nitro-7-pyrazolo[3,4-][1,2,3]triazine-2-oxide (), and several heat-resistant salts are synthesized through local structural modifications on . Comparison of thermal stability between and indicates that while the amino group has a negative impact on the thermal stability of , it enhances the detonation performance of and effectively reduces its mechanical sensitivity.
View Article and Find Full Text PDFInverse Electron Demand Diels-Alder-Type Heterocycle Syntheses with 1,2,3-Triazine 1-Oxides: Expanded Versatility.
Org Lett
February 2023
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States.
1,2,3-Triazine 1-oxides are remarkably effective substrates for inverse electron demand Diels-Alder reactions. Formed from vinyldiazoacetates via reaction with -butyl nitrite, these stable heterocyclic compounds undergo clean nucleophilic addition with amidines to form pyrimidines, with β-ketocarbonyl compounds and related nitrile derivatives to form polysubstituted pyridines and with 3/5-aminopyrazoles to form pyrazolo[1,5-]pyrimidines, in high yield. These practical reactions are rapid at room temperature, are base catalyzed, and offer a diversity of structural modifications.
View Article and Find Full Text PDFSynthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes.
Beilstein J Org Chem
November 2021
Institute of Biological and Chemical Systems - Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology, Campus North, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
We describe the synthesis of so far synthetically not accessible 3,6-substituted-4,6-dihydro-3-pyrazolo[3,4-][1,2,3]triazines as nitrogen-rich heterocycles. The target compounds were obtained in five steps, including an amidation and a cyclative cleavage reaction as key reaction steps. The introduction of two side chains allowed a variation of the pyrazolo[3,4-][1,2,3]triazine core with commercially available building blocks, enabling the extension of the protocol to gain other derivatives straightforwardly.
View Article and Find Full Text PDFPyrazolotriazines: Biological activities, synthetic strategies and recent developments.
Eur J Med Chem
November 2021
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:
Heterocyclic compounds create an important class of molecules that demonstrates various chemical spaces for the definition of effective medicines. Many N-heterocycles display numerous biological activities. Among condensed heterocycles, pyrazolotriazine derivatives have received the attention of researchers owing to the extensive spectrum of biological activities.
View Article and Find Full Text PDFSynthesis, antimicrobial, anti-proliferative activities, molecular docking and DFT studies of novel pyrazolo[5,1-c][1, 2, 4]triazine-3-carboxamide derivatives.
J Biomol Struct Dyn
December 2022
Department of Chemistry, Faculty of Science, Cairo University, Giza, Cairo, Egypt.
In this investigation, we studied the reactivity of 5-aminouracil () with ethyl cyanoacetate () utilizing microwave irradiation to afford the corresponding 2-cyano--(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide () in excellent yield. The electrophilic azo-coupling reaction of acetamide with aromatic diazonium salts afforded the corresponding hydrazone derivatives The Michael addition cyclization of hydrazone in pyridine to give pyrazolo[5,1-c][1, 2, 4]triazine-3-carboxamide derivatives. The obtained compounds were elucidated against antimicrobial activity and antitumor activity breast cancer cells (MCF-7) and liver cancer cells (HepG2) utilized MTT assay.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!