title: Novel biologically active nitro and amino substituted benzimidazo[1,2-a]quinolines.
abstract: This manuscript described the synthesis and biological activity of novel nitro substituted E-2-styryl-benzimidazoles and E-2-(2-benzimidazolyl)-3-phenylacrylonitriles and nitro and amino substituted benzimidazo[1,2-a]quinolines (4-5, 6-11, 17-20, and 21-32). All of the compounds showed significant growth inhibitory effect towards five tumor cell lines, whereby the IC(50) concentrations of 11, 20, 28, 29, 30, 32 are in the low micromolar range (IC(50)=2-19 μM). The DNA binding experiments did not show significant affinity of two selected compounds towards ct-DNA. The flow cytometry analysis of potential cell cycle perturbations after the treatment with compounds 9, 11, 25, and 29 demonstrated that all of the compounds (5 μM ≈ IC(50)) significantly delayed the progression through G1 phase, as demonstrated by the accumulation of cells in G1 phase, accompanied with the reduction of the cell number in the cells in S phase, which does not point to DNA damage as the main mechanism of action. Also, fluorescence microscopy study showed cytoplasmic distribution of the compounds, demonstrating that DNA is not the primary target of compounds. Thus, considerable antiproliferative effects of studied compounds are due to interactions with other biological targets within cells.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev Trg 20, PO Box 177, HR-10000 Zagreb, Croatia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Perin
authors.forename: Lidija
authors.initials: L
authors.lastname: Uzelac
authors.forename: Ivo
authors.initials: I
authors.lastname: Piantanida
authors.forename: Grace
authors.initials: G
authors.lastname: Karminski-Zamola
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.forename: Marijana
authors.initials: M
authors.lastname: Hranjec
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D004273:DNA, Neoplasm; D011804:Quinolines