Regioselective synthesis and evaluation of 2-amino 3-cyano chromene-chrysin hybrids as potential anticancer agents |
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| Affiliation: | 1. Guizhou Medicine Edible Plant Resources Research and Development Center, Guizhou University, Guiyang 550025, China;2. College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China;1. Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland;2. Department of Pharmaceutical Microbiology, Centre for Preclinical Research and Technology (CePT), Faculty of Pharmacy, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland;1. Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;2. Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;3. Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;4. Departamento de Química Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;5. Instituto de Tecnologia em Fármacos - Far-Manguinhos, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;6. Department of Chemistry, University of Aberdeen, Old Aberdeen, Scotland, UK;7. CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5 NY, Scotland, UK;1. Drug Discovery and Research Laboratory, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India;2. Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, 136119, India;1. College of Pharmaceutical Sciences, Guizhou University of Chinese Medicine, Guiyang, Guizhou 550025, China;2. Guizhou Medicine Edible Plant Resources Application Development Engineering Laboratory, Guizhou University, Guiyang 550025, China;1. Department of Drug Discovery and Development, Harrison School of Pharmacy, 4306 Walker Building, Auburn University, Auburn, AL 36849, USA;2. Department of Chemistry and Biochemistry, College of Sciences and Mathematics, 179 Chemistry Building, Auburn University, Auburn, AL 36849, USA;3. Drug Discovery Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom;4. Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia |
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| Abstract: | The first example of Ca(OH)2-activated p-regioselective synthesis of chrysin-fused chromene was reported through a cascade Michael/cyclization of chrysin and arylidenemalononitrile. The newly synthesized structurally diverse 2-amino 3-cyano chromene-chrysin hybrids 3 were evaluated for their in vitro anticancer activity, and some of the compounds showed stronger anti-proliferative activity against K562, PC-3, A549 and NCI-H1299 than parent compound chrysin, and demonstrated equipotent potency compared with the reference drug of cisplatin. In particular, compound 3h had the highest cytotoxicity towards K562 cells (IC50 = 6.41 µM). Furthermore, compound 3h induced apoptosis of K562 cells in a concentration-dependent manner, as well as induced the apoptosis possibly through promoting the formation of apoptotic DNA of cancer cell via the intrinsic apoptotic pathway. Thus, our results provide in vitro evidence that compound 3h may be a potential candidate for the development of new anti-tumour drugs. |
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| Keywords: | Chrysin 2-Amino 3-cyano chromene Regioselective Hybrids Anticancer agents |
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