Synthesis and evaluation of anti-tumor activity of novel triazolo[1,5-a] pyrimidine on cancer cells by induction of cellular apoptosis and inhibition of epithelial-to-mesenchymal transition process.

Publication date: Mar 17, 2020

Cancer is a leading cause of human death worldwide. One of the greatest challenges in cancer therapy is the discovery and design of novel products with potential anti-tumor activities. In this study, a new protocol involves three-component condensation of the 3-amino-1,2,4-triazole as a 1,3-binucleophile, versatile aldehydes and N-methyl-1-(methylthio)-2-nitroethenamine as an enamine analogous in the presence of trichloroacetic acid as a Bronsted-Lowry acidic promoter leads to new functionalized N-alkyl-6-nitro-3,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine in moderate to good yields. The presence of five nitrogen heteroatoms in the product structure has gathered immense attention among chemists and biologists due to their biological values. Therefore, we evaluated the anti-tumor activity of our synthetic compounds on different cancer cells including human malignant melanoma cells (A375), prostate cancer cells (PC3 cells, LNCaP cells) and normal cells HDF (human dermal fibroblast). Notably, we found that compound 4b that contains a nitro group has the best anti-tumor activity on three different cancer cells. By using DAPI staining, we showed cancer cells death. Apoptosis induction was shown using quantitative real time PCR (qRT-PCR) by evaluating of Bax and Bcl2 mRNA levels. Finally, we demonstrated that 4b has epithelial-to-mesenchymal transition (EMT) inhibition effect on cancer cells (by induction of E-cadherin and reduction of vimentin mRNA expression levels as two potential EMT markers). So, 4b could be an anti-cancer promising drug. Although, in vivo experiments will be required to evaluate possible side effects.

Safari, F., Bayat, M., Nasri, S., and Karami, S. Synthesis and evaluation of anti-tumor activity of novel triazolo pyrimidine on cancer cells by induction of cellular apoptosis and inhibition of epithelial-to-mesenchymal transition process. 26204. 2020 Bioorg Med Chem Lett.

Concepts Keywords
Aldehydes Therapy design products
Alkyl Cancer
Amine Synthesis anti tumor
Apoptosis Potential anti tumor
Bax Branches of biology
Bcl2 Cancer research
Cadherin Oncogenes
Cancer Epithelial–mesenchymal transition
Condensation Pathology
DAPI C-Met
EMT Vimentin
Enamine Bcl-2
Epithelial PC3
Heteroatoms Condensation
Lowry Apoptosis
Malignant Melanoma
Mesenchymal
Methyl
MRNA
Nitro
Nitro Group
Nitrogen
PCR
Prostate
Protocol
Pyrimidine
Staining
Triazole
Trichloroacetic Acid
Tumor
Vimentin
Vivo

Semantics

Type Source Name
disease MESH tumor
pathway KEGG Apoptosis
disease MESH death
drug DRUGBANK 1 2 4-Triazole
drug DRUGBANK Nitrogen
disease MESH malignant melanoma
disease MESH prostate cancer
pathway KEGG Prostate cancer

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