SÍNTESE DE NOVOS 1,2,3-TRIAZÓIS INSPIRADOS NO SRPIN340 E AVALIAÇÃO DE SEUS EFEITOS EM LINHAGEM CELULAR DE GLIOBLASTOMA HUMANO
It is herein described the synthesis of a series of thirty novel 1,2,3-triazole-1,4 disubstituted compounds inspired on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and biological evaluation of them against human glioblastoma multiforme cell line U87MG. Starting with 1-fluoro-2 nitro-4-(trifluoromethyl)benzene (1), the substances were prepared via a five-step synthetic route. The crucial step corresponded to the copper-catalyzed cycloaddition reaction between trifluoromethyl phenyl azides and different alkynes. In general, the compounds were obtained with good yields and they were characterized utilizing spectroscopic (IR and NMR) and spectrometric (HRMS) techniques. The evaluation of the synthesized compounds at three different treatment time (24 h, 48 h, and 72 h) and concentrations (50, 100, and 150 µmol L-1) revealed that five derivatives were capable of reducing cell viability by 50% after 72 h of treatment at the highest concentration. On the contrary, three derivatives significantly increased cell viability being this effect more pronounced after 48 h of treatment. In this regard, it stands out the compound 2-((1-(2-morpholino-5-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)isoindoline-1,3-dione (7) which increased cell viability in approximately 300% after 48 h of treatment at 100 µmol L-1. The substances that increased cell viaiblity present as common structural features the presence of a saturated nitrogen-containing six-membered ring and carbonylated fragments.
| Main Authors: | , , , , , , , , , , , |
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| Format: | Digital revista |
| Language: | Portuguese |
| Published: |
Sociedade Brasileira de Química
2021
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| Online Access: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-40422021001001268 |
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| Summary: | It is herein described the synthesis of a series of thirty novel 1,2,3-triazole-1,4 disubstituted compounds inspired on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and biological evaluation of them against human glioblastoma multiforme cell line U87MG. Starting with 1-fluoro-2 nitro-4-(trifluoromethyl)benzene (1), the substances were prepared via a five-step synthetic route. The crucial step corresponded to the copper-catalyzed cycloaddition reaction between trifluoromethyl phenyl azides and different alkynes. In general, the compounds were obtained with good yields and they were characterized utilizing spectroscopic (IR and NMR) and spectrometric (HRMS) techniques. The evaluation of the synthesized compounds at three different treatment time (24 h, 48 h, and 72 h) and concentrations (50, 100, and 150 µmol L-1) revealed that five derivatives were capable of reducing cell viability by 50% after 72 h of treatment at the highest concentration. On the contrary, three derivatives significantly increased cell viability being this effect more pronounced after 48 h of treatment. In this regard, it stands out the compound 2-((1-(2-morpholino-5-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)isoindoline-1,3-dione (7) which increased cell viability in approximately 300% after 48 h of treatment at 100 µmol L-1. The substances that increased cell viaiblity present as common structural features the presence of a saturated nitrogen-containing six-membered ring and carbonylated fragments. |
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