title: Synthesis and antiproliferative activity in vitro of novel 1,5-benzodiazepines. Part II.
abstract: The reaction of 2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1-cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (3) and 1-cinnamoyl-2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i-PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1-6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7-Carboxy-2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (7) was synthesized and its crystals were subjected to X-ray analysis. Benzodiazepines 1-6 were evaluated for antiproliferative activity in vitro. Among the compounds tested, 4-6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF-7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer).
authors.affiliation: Department of Technology of Drugs, Wroclaw University of Medicine, Nankier Sq. 1, 50-140 Wroclaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Nawrocka
authors.forename: B
authors.initials: B
authors.lastname: Sztuba
authors.forename: A
authors.initials: A
authors.lastname: Opolski
authors.forename: J
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: M W
authors.initials: MW
authors.lastname: Kowalska
authors.forename: T
authors.initials: T
authors.lastname: Głowiak
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001569:Benzodiazepines