title: Pyrrolo[1,2-b][1,2,5]benzothiadiazepines (PBTDs): A new class of agents with high apoptotic activity in chronic myelogenous leukemia K562 cells and in cells from patients at onset and who were imatinib-resistant.
abstract: Pyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxides (PBTDs) induced apoptosis in human BCR-ABL-expressing leukemia cells. The apoptotic activity was also observed in primary leukemic blasts, obtained from chronic myelogenous leukemia (CML) patients at onset or from patients in blast crisis and who were imatinib-resistant. Compounds 5 and 14 induced apoptosis before BCR-ABL protein expression and tyrosin phosphorylation were affected and activated different caspases in the apoptotic pathway. PBTDs are a new class of valid candidates for the treatment of CML.
authors.affiliation: Dipartimento di Studi Farmaceutici, Università La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy. romano.silvestri@uniroma1.it
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marfè
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Morgante
authors.forename: Manuela
authors.initials: M
authors.lastname: Morgante
authors.forename: Carla
authors.initials: C
authors.lastname: Di Stefano
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Catalano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Filomeni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ciriolo
authors.forename: Matteo Antonio
authors.initials: MA
authors.lastname: Russo
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.forename: Francesco
authors.initials: F
authors.lastname: La Torre
authors.forename: Paola
authors.initials: P
authors.lastname: Sinibaldi Salimei
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001549:Benzamides; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000473:pathology*; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D013841:Thiazepines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases