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 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.
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil.
Marcio M
MM
Lobo
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Anexo II, 90050-170, Porto Alegre, RS, Brazil.
Cassiana M
CM
Viau
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil.
Josiane M
JM
Dos Santos
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil.
Helio G
HG
Bonacorso
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil.
Marcos A P
MA
Martins
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Anexo II, 90050-170, Porto Alegre, RS, Brazil.
Simone S
SS
Amaral
Laboratório de Genética Toxicológica, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Anexo II, 90050-170, Porto Alegre, RS, Brazil. Electronic address: jenifers@ufcspa.edu.br.
Jenifer
J
Saffi
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97105-900, Santa Maria, Brazil. Electronic address: nilo.zanatta@ufsm.br.
Nilo
N
Zanatta
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007555:Isoxazoles; D011744:Pyrimidinones
4,5-Dihydroisoxazoles; Antiproliferative activity; Human tumoral cell; Nitrile oxides; Pyrimidin-2-ones