Abstract
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•Synthesis of two novel series of isoxazole and triazole tyrosol derivatives.•A regiospecific synthesis was developed using microwave irradiation condition.•Derivatives exhibited anticancer effect against human glioblastoma cancer cells.•The anticancer activity was exerted through induction of apoptosis.•Most compounds displayed low antibacterial and hemolytic activities.
Two series of 3,5-disubstituted isoxazoles (6a–e) and 1,4-disubstituted triazoles (8a–e) derivatives have been synthesized from tyrosol (1), a natural phenolic compound, detected in several natural sources such as olive oil, and well-known by its wide spectrum of biological activities. Copper-catalyzed microwave-assisted 1,3-dipolar cycloaddition reactions between tyrosol-alkyne derivative 2 and two series of aryl nitrile oxides (5a–e) and azides (7a-e) regiospecifically afforded 3,5-disubstituted isoxazoles (6a–e) and 1,4-triazole derivatives (8a–e), respectively in quantitative yields. Synthesized compounds were purified and characterized by spectroscopic means including 1D and 2D NMR techniques and HRMS analysis. The newly prepared hybrid molecules have been evaluated for their anticancer and hemolytic activities. Results showed that most derivatives displayed significant antiproliferative activity against human glioblastoma cancer cells (U87) in a dose-dependent manner. Compounds 6d (IC50 = 15.2 ± 1.0 μg/mL) and 8e (IC50 = 21.0 ± 0.9 μg/mL) exhibited more potent anticancer activity. Moreover, most derivatives displayed low hemolytic activity, even at higher concentrations which suggested that these classes of compounds are suitable candidates for further in vivo investigations. The obtained results allow us to consider the newly synthesized isoxazole- and triazole-linked tyrosol derivatives as promising scaffolds for the development of effective anticancer agents.