Elena Chugunova1,2, Gabriele Micheletti3, Dario Telese3, Carla Boga3, Daut Islamov1, Konstantin Usachev4, Alexander Burilov1,2, Alena Tulesinova5, Alexandra Voloshina1, Anna Lyubina1, Syumbelya Amerhanova1, Tatiana Gerasimova1, Aisylu Gilfanova1, Victor Syakaev1. 1. FRC Kazan Scientific Center, Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, 420088 Kazan, Russia. 2. Laboratory of Plant Infectious Diseases, FRC Kazan Scientific Center of Russian Academy of Sciences, 420111 Kazan, Russia. 3. Department of Industrial Chemistry 'Toso Montanari', Alma Mater Studiorum-Universita di Bologna Viale Del Risorgimento, 40136 Bologna, Italy. 4. Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of Russian Academy of Sciences, 420111 Kazan, Russia. 5. Institute of Chemical Engineering and Technology, Kazan National Research Technological University, 420015 Kazan, Russia.
Abstract
A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.
A series of novel hybrid compounds containing benzofuroxan and n class="Chemical">2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.
Authors: Elena Chugunova; Timur Shaekhov; Ayrat Khamatgalimov; Vladimir Gorshkov; Alexander Burilov Journal: Int J Mol Sci Date: 2022-01-27 Impact factor: 5.923