title: Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogues.
abstract: Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contrast, a derivative of the latter series elicited distinct responses in accordance with the dose. Thus, low concentrations (GI30) induced morphological changes characteristic of autophagic death with massive formation of cytoplasmic acid vacuoles without apparent loss of nuclear material, and with arrest of cell cycle at the G1 phase, whereas higher concentrations (GI70) induced apoptosis with arrest of cell cycle at the G1 phase.
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. anna.carbone@unipa.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. barbara.parrino@unipa.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Parrino
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. gloria.divita@unipa.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Di Vita
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. alessandro.attanzio@unipa.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Attanzio
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. virginia.spano@unipa.it.
authors.forename: Virginia
authors.initials: V
authors.lastname: Spanò
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. alessandra.montalbano@unipa.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Montalbano
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. paola.barraja@unipa.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Barraja
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. luisa.tesoriere@unipa.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Tesoriere
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. maria.livrea@unipa.it.
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Livrea
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. patrizia.diana@unipa.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, via Archirafi 32, 90123 Palermo, Italy. girolamo.cirrincione@unipa.it.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016195:G2 Phase / Q000187:drug effects; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D011725:Pyridines; D011758:Pyrroles; D013844:Thiazoles