Design, Synthesis and Biological Evaluation of the Novel Antitumor Agent 2H-benzo[b][1, 4]oxazin-3(4H)-one and Its Deriv
In order to further explore the potential pharmaceutical application of the benzoxazine type molecules, a series of novel 4 and 6 substituted 2H-benzo[b][1, 4]-oxazin-3(4H)-one derivatives were prepared by a convenient Microwave-assistant four-step synthe
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Design, Synthesis and Biological Evaluation of the Novel Antitumor Agent 2H-benzo[b][1, 4]oxazin-3(4H)-one and Its Derivatives Huanhuan Li, Kailin Han, Qiannan Guo, Fengxi Liu, Peng Yu and Yuou Teng Abstract In order to further explore the potential pharmaceutical application of the benzoxazine type molecules, a series of novel 4 and 6 substituted 2H-benzo[b] [1, 4]-oxazin-3(4H)-one derivatives were prepared by a convenient Microwaveassistant four-step synthetic approach in 20–30 % overall yield. All the newly synthesized compounds were characterized by 1H NMR and 13C NMR. 7 of the 8 target compounds among them have not been reported yet. The primary antitumor activities of the target compounds and key intermediates against HT-29, K562 and HepG2 cell lines have been evaluated and result of the test shows that 6 benzoxazine derivatives demonstrated certain inhibition against those tumor cells, especially 6-bromo-4-(4-(trifluoromethyl)benzyl)-2H-benzo[b][1, 4]oxazin-3(4H)-one possessed good antitumor activity against HepG2 cancer cell with an IC50 of 6 lM. Keywords Benzoxazine
Heck reaction Antitumor activity
382.1 Introduction WHO survey data shows that cancer is the second leading cause of death after cardiovascular diseases [1]. At present, cancer mortality rate is still on the rise. The existing chemotherapy drugs kill cancer cells mostly by interfering cell division.
H. Li K. Han Q. Guo F. Liu P. Yu Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, People’s Republic of China Y. Teng (&) Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, 300457 Tianjin, People’s Republic of China e-mail: [email protected]
S. Li et al. (eds.), Frontier and Future Development of Information Technology 3003 in Medicine and Education, Lecture Notes in Electrical Engineering 269, DOI: 10.1007/978-94-007-7618-0_382, Springer Science+Business Media Dordrecht 2014
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As the phenomenon of resistance gradually emerged in clinical practice using anti-cancer drugs, there is an urgent need for more effective anti-cancer drugs. Benzoxazine-based compounds are a large class of novel heterocyclic compounds and possess a wide range of biological activities, such as antitumor [2], anti-inflammatory [3], antiulcer [4]. 2H-benzo[b][1, 4]oxazin-3(4H)-one derivatives also exhibit other bioactivities, such as antipyretic [5], antihypertensive [6], antifungal [7] and potassium channel modulators [8] and so on [9, 10], which attracts the interest of many research groups. Previous studies of 2H-benzo[b][1, 4]oxazin-3(4H)-one derivatives were mainly focused on the substitution at 2 and 4 positions, but the substitution at 4 and 6 positions of Benzoxazine was rarely reported. In this paper, we would like to report the design and Microwave-assistant four-step synthesis of novel 4- and 6-substituted 2H-benzo[b][1, 4]oxazin-3(4H)-one analogues as we
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