title: 3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors.
abstract: During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to be of a potency comparable to etoposide and greater than 6-mercaptopurine in all cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6-dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was conducted in order to extend the studies of structure-activity relationship (SAR) for this class of molecules. With the aim to evaluate if 3-aryl-2-[1H-benzotriazol-1-yl]acrylonitriles were able to act like tubulin binding agents, the effects on cell cycle distribution of the most active compounds (1, 2a, 3 and 4) were analyzed in K562 cells. A detailed molecular modeling study of the putative binding mode of this series of compounds on tubulin is also reported.
authors: Dipartimento Scienze del Farmaco, Università degli Studi di Sassari, Via Muroni 23/a, 07100 Sassari, Italy. acarta@uniss.it
authors: Antonio
authors: A
authors: Carta
authors: Irene
authors: I
authors: Briguglio
authors: Sandra
authors: S
authors: Piras
authors: Giampiero
authors: G
authors: Boatto
authors: Paolo
authors: P
authors: La Colla
authors: Roberta
authors: R
authors: Loddo
authors: Manlio
authors: M
authors: Tolomeo
authors: Stefania
authors: S
authors: Grimaudo
authors: Antonietta
authors: A
authors: Di Cristina
authors: Rosaria Maria
authors: RM
authors: Pipitone
authors: Erik
authors: E
authors: Laurini
authors: Maria Silvia
authors: MS
authors: Paneni
authors: Paola
authors: P
authors: Posocco
authors: Maurizio
authors: M
authors: Fermeglia
authors: Sabrina
authors: S
authors: Pricl
mesh_terms: D000181:Acrylonitrile / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D002453:Cell Cycle; D003078:Colchicine / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D014404:Tubulin / Q000187:drug effects*
chemical_list: D014230:Triazoles; D014404:Tubulin; C012771:benzotriazole; D000181:Acrylonitrile; D003078:Colchicine