Anti-Cancer Agents in Medicinal Chemistry
Anti-Cancer Agents in Medicinal Chemistry
Anti-Cancer Agents in Medicinal Chemistry, 2015, 15, 131-136 131Potential Anticancer Agents. I. Synthesis of Isoxazole Moiety Containing QuinazolineDerivatives and Preliminarily in vitro Anticancer ActivityJian-Ping Yong#, Can-Zhong Lu#,* and Xiaoyuan WuKey Laboratory of Design and Assembly of Functional Nanostructures, Chinese Academy of Sciences of P. R. China, Fuzhou, 350002, P. R. China[pic 2][pic 3][pic 4][pic 5]Abstract: 14 new structures of isoxazole-moiety-containing quinazoline derivatives(3a~3n) were synthesized for the first time and characterized by IR, 1H NMR, 13C NMR, ESI-MS. Subsequently, their in vitro anticancer activity against A549, HCT116 and MCF-7 cell lines was preliminarily evaluated using the MTT method. Among them, most compounds showed good to excellent anticancer activity, especially 3d, 3i, 3k and 3m exhibited the more potent anticancer activity against A549, HCT116 and MCF-7 cell lines, which can be regarded as the promising drug candidates for development of anticancer drugs.Keywords: Anticancer activity, isoxazole moiety, quinazoline derivatives, synthesis.#Author’s Profile: Jian-Ping Yong was born in Ningxia, China. He graduated in applied Chemistry from Ningxia University (2002), and finished his Ph. D. in Organic Chemistry under the supervision of Prof. Haji Akber Aisa at Xinjiang Technical Institute of Physics and Chemistry(2008). Then, he worked as an assistant professor in Ningxia Medical University (2009-2011). After postdoctoral studies with Professor CanzhongLu at Fujian Institute of Research on the Structure of Matter (2011-2013), he joined prof. Lu’s group and became an associate professor in 2014. His interests include drug design and synthesis, Natural Product Chemistry.#Author’s Profile: Prof. Can-Zhong Lu was born in Fujian, China. He graduated in Chemistry from Xiamen University (1986). Then, he worked in Fujian Institute of Research on the Structure of Matter (1986-1992). He received his Ph.D. under the supervision of Prof. J. R. Dilworth at the University of Essex, UK. (1996). After postdoctoral studies in Department of Chemistry at Bielefeld University, Germany (1996-1998), he started his independent academic career at FJIRSM, then became a Full Professor in 2002, and has published more than 250
SCI papers. His current research interests include synthesis, structural characterization and catalysis of polyoxometalates-based coordination polymer; luminescent materials and devices based on Cu(I); drug design and synthesis.INTRODUCTIONCancer is the second most lethal disease with the abnormal cellular proliferation and metastasis, second only to the cardiovascular and cerebrovascular disease in the world. Cancer types include lung cancer, gastric cancer, liver cancer, colon cancer, breast cancer and non-small cell lung cancer (NSCLC) etc.. Lung cancer causes a fifth of all cancer-related deaths [1], while NSCLC accounts for most cases of lung cancer, and it is usually diagnosed in advanced stages [2]. The great cancer incidence worldwide increases the search for new, safer and efficent anticancer agents, aiming the prevention or the cure of this illness.Quinazoline core is the best scaffolds for development of anticancer agents [3]. Some quinazolines as anticancer agents have been used in clinics: Gefitinib(IressaTM, AstraZeneca), Erlotinib(TarcevaTM, Genentech) and Lapatinib(TykerbTM, GlaxoSmithKline) (Fig. 1) have been approved by FDA for treatment of cancer. 4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4-quinazoline (Conmana®,Zhejiang Beta Pharma Co. Ltd., China) (Fig. 1), named as Icotinib, is another quinazoline derivative, which mimics erlotinib with a crown ether rused quinazoline moiety. The phase III clinical study for treatment of advanced NSCLC showed that Icotinib exhibited the equal therapeutic efficacy and low toxicity to gefitinib [4]. It has been approved by China Food and Drug Administration(CFDA) in 2011 for treatment of cancer in clinics.The isoxazole moiety, as a potential functional group, is usually introduced into some drug molecules to improve their biological activities [5-12]; In our previous work, we introduced the isoxazole moiety at C-30 position of glycyrrhetinic acid(GTA) and 11- deoxyglycyrrhetinic acid(DGTA), and synthesized a series of*Address correspondence to this author at the Key Laboratory of Design and Assembly of Functional Nanostructures, Chinese Academy of Sciences of P. R. China, Fuzhou, 350002, P. R. China; Fax: +86 59183705794;[pic 6]