title: Inhibition of 'in vitro' tumor cell growth by aromatic polyamidines exhibiting antiproteinase activity.
abstract: Aromatic polyamidines containing two, three or four benzamidine residues inhibit proteinase activity and proliferation of different human tumor cell lines, including leukemic (K562, HEL), melanoma (Colo 38) and B-lymphoid (WI-L2) cell lines. In addition, the benzamidine derivatives analysed in the present study inhibit cell growth of the Chinese hamster FHO6T1-1 cell line, obtained after transfection of primary lung cells with the activated human T24-Ha-ras-1 oncogene. After treatment of FHO6T1-1 cells with benzamidine derivatives, a sharp decrease of the content of Ha-ras-1 mRNA was found, but not of transferrin receptor mRNA. We found that inhibition of cell proliferation by tetra-benzamidine derivatives is not restricted to tumor cells, but concerns also non-tumorigenic cell lines as well as normal primary fibroblasts. Therefore, our analysis was extended to di- and tri-benzamidine derivatives, which could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors. The data obtained demonstrate that these latter compounds and their halo-derivatives also exhibit strong antiproliferative effects on in vitro cultured cells.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: G
authors.initials: G
authors.lastname: Feriotto
authors.forename: D
authors.initials: D
authors.lastname: Spandidos
authors.forename: R
authors.initials: R
authors.lastname: Ferroni
authors.forename: M
authors.initials: M
authors.lastname: Guarneri
authors.forename: R
authors.initials: R
authors.lastname: Barbieri
authors.forename: R
authors.initials: R
authors.lastname: Gambari
mesh_terms: D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001550:Benzamidines / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000578:Amidines; D001550:Benzamidines; D011480:Protease Inhibitors; D012333:RNA, Messenger; C057885:1,3-di-(4-amidinophenoxy)-2,2-bis-(4-amidinophenoxymethyl)propane; C057886:4,4'-(2,2-bis((4-(aminoiminomethyl)-2-bromophenoxy)methyl)-1,3-propanediyl)bis(oxy))bis(3-bromobenzenecarboximidamide; C005555:propamidine; C032157:benzamidine