title: Synthesis, antitumor activity, and structure-activity relationship of some benzo[a]pyrano[2,3-c]phenazine derivatives.
abstract: A series of benzo[a]pyrano[2,3-c]phenazine derivatives with a wide range of substitutions at ring C of the benzophenazine were designed and synthesized using the one-pot, four-component domino reactions. The targeted compounds were evaluated for their antitumor activities against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro. The most active compound 6{1,2,1,9} featured the CN and p-dimethylamino phenyl substituents on γ-pyran structure on ring C. Significantly, compound 6{1,2,1,9} was found to have the highest growth inhibitory activity against the HepG2 cell line with IC50 values of 6.71 µM, which was 1.6-fold more potent than positive control anticancer drug Hydroxycamptothecine (HCPT). Furthermore, structure-activity relationship (SAR) studies on the substitutions at ring C were discussed in details.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Xue
authors.initials: X
authors.lastname: Tong
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yan
authors.forename: Daichun
authors.initials: D
authors.lastname: Liu
authors.forename: Wanjing
authors.initials: W
authors.lastname: Li
authors.forename: Shengyu
authors.initials: S
authors.lastname: Qi
authors.forename: Dake
authors.initials: D
authors.lastname: Xiao
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Engineering, China Pharmaceutical University, Nanjing, Jiangsu 210009, China. jiangfeng@cpu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001577:Benzophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; D010619:Phenazines; C047723:benzophenone