title: Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b]isoquinoline derivatives, synthesis and biological activity.
abstract: A series of linear pyrrolo[1,2-b]isoquinoline derivatives was synthesized for antitumor evaluation. The preliminary antitumor studies reveal that both bis(hydroxymethyl) and their bis(alkylcarbamate) derivatives show significant antitumor activity in inhibiting various human tumor cell growth in vitro. 1,2-Bis(hydroxymethyl)-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline (20a) was selected for antitumor studies in animal models. The results show that this agent can induce complete tumor remission or significant suppression in nude mice bearing human breast (MX-1) xenograft and ovarian (SK-OV-3) xenografts, respectively. Alkaline agarose gel shifting assay showed that 20a is able to cross-link with DNA. Studies on the cell cycle inhibition revealed that this agent induces cell arrest at G2/M phase. The results warrant further antitumor investigation against other human tumor growth in animal models.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ravi
authors.initials: R
authors.lastname: Chaniyara
authors.forename: Naval
authors.initials: N
authors.lastname: Kapuriya
authors.forename: Huajin
authors.initials: H
authors.lastname: Dong
authors.forename: Pei-Chih
authors.initials: PC
authors.lastname: Lee
authors.forename: Sharda
authors.initials: S
authors.lastname: Suman
authors.forename: Bhavin
authors.initials: B
authors.lastname: Marvania
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kakadiya
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
authors.forename: Tsann-Long
authors.initials: TL
authors.lastname: Su
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007546:Isoquinolines