title: Synthesis and evaluation of antitumor activity of novel N-acyllavendamycin analogues and quinoline-5,8-diones.
abstract: A series of 7-N-acyllavendamycins with zero, one or two substituents at the C-2', C-3', and C-11' were synthesized through short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with tryptamine or tryptophans produced the desired lavendamycins. Screening data on a panel of three ras oncogene-transformed cell lines and the non-transformed parent cell line showed that a significant number of these analogues are potent antitumor agents and appear to be particularly active against K-ras transformed cells. Compared with the corresponding quinolinediones, these novel lavendamycins are much more inhibitory toward the transformed cells indicating that the beta-carboline moiety of the lavendamycin analogues plays an important role in its potency and selective toxicity.
authors.affiliation: Chemistry Department, Ball State University, Muncie, IN 47306, USA. mbehforo@bsu.edu
authors.forename: Mohammad
authors.initials: M
authors.lastname: Behforouz
authors.forename: Wen
authors.initials: W
authors.lastname: Cai
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Mohammadi
authors.forename: Mark G
authors.initials: MG
authors.lastname: Stocksdale
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Gu
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ahmadian
authors.forename: Darric E
authors.initials: DE
authors.lastname: Baty
authors.forename: Michele R
authors.initials: MR
authors.lastname: Etling
authors.forename: Charmaine H
authors.initials: CH
authors.lastname: Al-Anzi
authors.forename: Tyson M
authors.initials: TM
authors.lastname: Swiftney
authors.forename: Lee R
authors.initials: LR
authors.lastname: Tanzer
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Merriman
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Behforouz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013308:Streptonigrin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines; D013308:Streptonigrin; C034566:lavendamycin