title: Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potent anti-tumor agents.
abstract: A series of phenanthroindolizidine and phenanthroquinolizidine alkaloids and their 14-amino-derivatives (1-44) were prepared and systematically evaluated for their anti-tumor activities against A549 and HL60 cell lines. The bioassay results showed that most of these alkaloids possess good anti-tumor activities. Especially, compounds 15, 22, 28, 33-36, 40 and 42 displayed low nanomolar or subnanomolar levels of anti-tumor activity. The configuration of (13aS,14S)-14-hydroxyphenanthroindolizidines and (14aR,15R)-15-hydroxyphenanthroquinolizidines was confirmed to be optimal. 14-Amino-phenanthroindolizidines with increased polarity possess good anti-tumor activity, especially for compounds 26 and 28. Most of the phenanthroquinolizidine alkaloids exhibited higher anti-tumor activity than that of phenanthroindolizidine alkaloids. Our present study provides fundamental support for development and optimization of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potential anti-tumor drugs.
authors.affiliation: State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, 94 Weijing street, Nankai University, Tianjin 300071, China.
authors.forename: Ziwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Guifang
authors.initials: G
authors.lastname: Han
authors.forename: Fazhong
authors.initials: F
authors.lastname: Chen
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
authors.forename: Kailiang
authors.initials: K
authors.lastname: Wang
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.forename: Linghua
authors.initials: L
authors.lastname: Meng
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007212:Indolizines / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D011807:Quinolizines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D007212:Indolizines; D010618:Phenanthrolines; D011807:Quinolizines; C521640:phenanthroindolizidine; C521641:phenanthroquinolizidine