Synthesis and cytotoxic activity evaluation of some novel 1-(3-(aryl-4,5-dihydroisoxazol-5-yl)methyl)-4-trihalomethyl-1H-pyrimidin-2-ones in human cancer cells

The synthesis of a series of 14 new 1-(3-(aryl-4,5-dihydroisoxazol-5-yl)methyl)-4-trihalomethyl-1H-pyrimidin-2-ones from the 1,3-dipolar cycloaddition reaction of 1-allyl-4-(trihalomethyl)pyrimidin-2(1H)-ones with aryl nitrile oxides is described. Also, the antiproliferative activity of the title co...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2015-08, Vol.101, p.836-842
Main Authors: Lobo, Marcio M., Viau, Cassiana M., dos Santos, Josiane M., Bonacorso, Helio G., Martins, Marcos A.P., Amaral, Simone S., Saffi, Jenifer, Zanatta, Nilo
Format: Article
Language:English
Subjects:
4,5-Dihydroisoxazoles
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antiproliferative activity
Cell Line, Tumor
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HEK293 Cells
Human tumoral cell
Humans
Isoxazoles - chemical synthesis
Isoxazoles - chemistry
Isoxazoles - pharmacology
Models, Molecular
Molecular Structure
Nitrile oxides
Pyrimidin-2-ones
Pyrimidinones - chemical synthesis
Pyrimidinones - chemistry
Pyrimidinones - pharmacology
Structure-Activity Relationship
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Summary:The synthesis of a series of 14 new 1-(3-(aryl-4,5-dihydroisoxazol-5-yl)methyl)-4-trihalomethyl-1H-pyrimidin-2-ones from the 1,3-dipolar cycloaddition reaction of 1-allyl-4-(trihalomethyl)pyrimidin-2(1H)-ones with aryl nitrile oxides is described. Also, the antiproliferative activity of the title compounds was tested against five human tumoral cell lines: MCF-7 breast cancer cell line, ER+ (estrogen receptor positive); HepG-2 (hepatoma); T-24 (bladder cancer); HCT-116 cell (colorectal carcinoma); and CACO-2. The preliminary results are promising, since three compounds presented IC50 values below 2 μM, as well as moderate to high selectivity. [Display omitted] •Synthesis of dihydroisoxazolmethyl-pyrimidines from dipolar cycloaddition reaction.•Antiproliferative activity of dihydroisoxazol-5-yl-(methyl)-1H-pyrimidin-2-ones.•Antiproliferative activity of pyrimidines against five human tumoral cell lines.•Three derivatives showed high activity against HepG-2, T-24, and CACO-2.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2015.06.040