Current organic synthesis · 2019
A Novel Series of N-aryltriazole and N-acridinyltriazole Hybrids as Potential Anticancer Agents.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Rono Charles K, Darkwa James, Meyer Debra, Makhubela Banothile C E
Аннотация
BACKGROUND: Triazoles are a class of aza-heterocycles with broad spectrum of biological importance. The synthetic tunability of the triazole moiety allows for the development of new pharmacophores with applications as drugs to contend with the burden of cancer.
OBJECTIVE: In this study, we aimed to develop a series of N-aryltriazole and N-acridinyltriazole molecular hybrids and evaluate their potential as anticancer agents.
METHODS: The triazole derivatives (1-10) were synthesized via a tandem nucleophilic substitution of aryl chlorides with sodium azide followed by 1,3-dipolar cycloaddition of the resulting organic azides with terminal/internal alkynes. From terminal alkynes, the well established copper(I) catalyzed azide-alkynes 1,3- dipolar cycloaddition, a premier example of click chemistry, was employed to access the 1,4-regioisomers of N-benzyl-1H-1,2,3-triazoles and N-acridynyl-1H-1,2,3-triazoles. All the compounds thus synthesized were characterized by 1D and 2D NMR spectroscopy and high resolution mass spectrometry.
RESULTS: Thermally controlled 1,3-dipolar cycloaddition was used to deliver N-aryl-1H-1,2,3-triazoles with 1,4,5-substitution on the triazole framework. The unprecedented high regioselectivity promoted by the sterically-strained silylated 1,4,5-trisubstituted moiety 4a offers a useful synthetic precursor with the silyl group being a synthetic handle for further structural elaboration to the desired 1,(4),5-di(tri)substituted 1,2,3- triazoles. Notably, anticancer evaluation revealed good cytotoxic activities of the novel acridinyltriazole hybrids (6-10) at micromolar concentrations in the range of 12.5 µM-100 µM against cervical cancer HeLa, kidney cancer HEK293, lung cancer A549 and leukemic MT4 cancer cell lines (p < 0.05).
CONCLUSION: A series of novel triazole-based acridine hybrids have been developed as potential leads for the development of multifaceted anticancer agents.
OBJECTIVE: In this study, we aimed to develop a series of N-aryltriazole and N-acridinyltriazole molecular hybrids and evaluate their potential as anticancer agents.
METHODS: The triazole derivatives (1-10) were synthesized via a tandem nucleophilic substitution of aryl chlorides with sodium azide followed by 1,3-dipolar cycloaddition of the resulting organic azides with terminal/internal alkynes. From terminal alkynes, the well established copper(I) catalyzed azide-alkynes 1,3- dipolar cycloaddition, a premier example of click chemistry, was employed to access the 1,4-regioisomers of N-benzyl-1H-1,2,3-triazoles and N-acridynyl-1H-1,2,3-triazoles. All the compounds thus synthesized were characterized by 1D and 2D NMR spectroscopy and high resolution mass spectrometry.
RESULTS: Thermally controlled 1,3-dipolar cycloaddition was used to deliver N-aryl-1H-1,2,3-triazoles with 1,4,5-substitution on the triazole framework. The unprecedented high regioselectivity promoted by the sterically-strained silylated 1,4,5-trisubstituted moiety 4a offers a useful synthetic precursor with the silyl group being a synthetic handle for further structural elaboration to the desired 1,(4),5-di(tri)substituted 1,2,3- triazoles. Notably, anticancer evaluation revealed good cytotoxic activities of the novel acridinyltriazole hybrids (6-10) at micromolar concentrations in the range of 12.5 µM-100 µM against cervical cancer HeLa, kidney cancer HEK293, lung cancer A549 and leukemic MT4 cancer cell lines (p < 0.05).
CONCLUSION: A series of novel triazole-based acridine hybrids have been developed as potential leads for the development of multifaceted anticancer agents.