title: Synthesis and biological activity of alpha-bromoacryloyl lexitropsin conjugates.
abstract: The design, synthesis and biological evaluation of lexitropsins bearing mixed heterocyclic and benzoheterocyclic moieties and tethered to an alpha-bromo acrylic moiety acting as alkylating moiety are reported, and structure-activity relationships determined. With respect to antiproliferative activity against L1210 and K562 cells, compounds 7 and 10 showed the greatest potency, while compounds 4 and 5 exhibit the lowest activity. Among the synthesized compounds 4-12, the derivative 10 was found to be the most potent member of this class and it is 70-fold more active than the bis-pyrrole counterpart 3 against L1210 cell line. In addition, the cytotoxicity of derivatives 5-12 against KB cells and the influence of different glutathione (GSH) concentrations on the cytotoxic effects was also investigated.
authors: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17/19, 44100 Ferrara, Italy.
authors: Romeo
authors: R
authors: Romagnoli
authors: Pier Giovanni
authors: PG
authors: Baraldi
authors: Maria Antonietta
authors: MA
authors: Iaconinoto
authors: Maria Dora
authors: MD
authors: Carrion
authors: Mojgan Aghazadeh
authors: MA
authors: Tabrizi
authors: Roberto
authors: R
authors: Gambari
authors: Monica
authors: M
authors: Borgatti
authors: Jörg
authors: J
authors: Heilmann
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009429:Netropsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001572:Benzofurans; D006571:Heterocyclic Compounds; D007093:Imidazoles; D011720:Pyrazoles; D011758:Pyrroles; D013876:Thiophenes; C088015:benzothiophene; C053654:lexitropsin; D009429:Netropsin; C029899:imidazole