title: Synthesis and antiproliferative activity in vitro of new pyrido[1,4-b]diazepine derivatives and imidazo[4,5-b]pyridine.
abstract: A novel series of esters 8-10 and hydrazones 4-6 was synthesized from 4-aryl-2-phenacylidene-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepine (1-3). Subsequent treatment of hydrazone 4 with p-chlorbenzaldehyde furnished azine 7. Long-standing heating of ester 8 with hydrazine hydrate afforded 3-[1-(p-chlorophenylene)-2-(5-phenyl-1H-pyrazol-3-yl)-ethyl]-1,3-dihydroimidazo[4,5-b]pyridin-2-one (11). The structures of 4-6 and 8-10 were identified by the results of elemental analysis and their IR, 1H-NMR and MS spectra. Additionally, the structure of 11 was confirmed by X-ray diffraction method. Compounds 8-10 and 11 were examined for their antiproliferative activity in vitro against the cells of 5 human cancer cell lines, using SRB or MTT technique. Among tested compounds, only 11 revealed cytotoxic activity in vitro against all cell lines applied with ID50 (inhibitory dose 50%) values lower than 4 microg/mL, which is an international activity criterion for synthetic compounds. All compounds inhibit the proliferation of HL-60 human promyelocytic leukemia cell line.
authors.affiliation: Department of Technology of Drugs, Wroclaw University of Medicine, 1 Nankier Sq., 50-140 Wrocław, Poland. hanna@ktl.am.wroc.pl
authors.forename: Hanna
authors.initials: H
authors.lastname: Liszkiewicz
authors.forename: Wanda P
authors.initials: WP
authors.lastname: Nawrocka
authors.forename: Barbara
authors.initials: B
authors.lastname: Sztuba
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Jaroszewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Nasulewicz
authors.forename: Marzena
authors.initials: M
authors.lastname: Pełczyńska
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011725:Pyridines