title: Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin.
abstract: Eighteen symmetrical bis-Schiff base derivatives of isatin were synthesized by condensation of the natural or synthetic isatins with hydrazine and were evaluated for their in vitro and in vivo antitumor activities. More than half of the obtained compounds showed potent cytotoxicity according to the MTT assay on five different human cancer cell lines (i.e. HeLa, SGC-7901, HepG2, U251, and A549), with compound 3b 3,3'-(hydrazine-1,2-diylidene)bis (5-methylindolin-2-one) being the most potent compound on HepG2 (IC₅₀ ∼ 4.23 μM). 3b was also found to be able to inhibit substantially the tumor growth on the HepS-bearing mice at a dose of 40 mg/kg. The real-time live cell imaging and tracking in the H2B-labeled HeLa cells revealed that 3b could induce mitosis interference and apoptosis-associated cell death. In mechanism study, 3b arrested the cell cycle at the G2/M phase in HepG2 cells by down-regulating the expression of cyclin B1 and cdc 2.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Liang
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xia
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lei
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: qz_yao@yahoo.com.cn.
authors.forename: Qizheng
authors.initials: Q
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China. Electronic address: jinggao@ujs.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D007510:Isatin / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D012545:Schiff Bases / Q000737:chemistry* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D012545:Schiff Bases; D007510:Isatin
keywords: Antitumor; Apoptosis; Cytotoxicity; Isatin; Mitosis interference; Schiff base