title: Synthesis and Antineoplastic Evaluation of Novel Unsymmetrical 1,3,4-Oxadiazoles.
abstract: A series of novel 1,3,4-oxadiazoles was synthesized and evaluated for their cytotoxic activity in in vitro tumor models. Four of the new compounds (2d, 2j, 2k, and 2n) showed growth inhibition in the XTT dye assay. The most active agent, 2j, showed high potency against human cancer cells with IC50s ranging from 0.05 to 1.7 μM. Preliminary SAR correlations suggested that the nature of chains on the oxadiazole is important for antitumor potency in vitro. Compound 2j determined a G2/M arrest of the cell cycle and also activated a strong apoptotic response. The β-tubulin immunofluorescence analysis indicated that compound 2j effectively inhibited the microtubule organization in all cancer cell lines, causing the formation of abnormal spindle, which did not affect the normal human fibroblast cells NB1, Mrc-5 and IBR3. For all these reasons, compound 2j could be a good candidate in chemopreventive or chemotherapeutic strategies.
authors: Department of Biomedical Sciences, and National Institute of Biostructures and Biosystems, University of Sassari , 07100 Sassari, Sardinia, Italy.
authors: Valentina
authors: V
authors: Nieddu
authors: Department of Chemistry and Pharmacy, University of Sassari , Via Muroni 23, 07100 Sassari, Sardinia, Italy.
authors: Giansalvo
authors: G
authors: Pinna
authors: Department of Biomedical Sciences, and National Institute of Biostructures and Biosystems, University of Sassari , 07100 Sassari, Sardinia, Italy.|Kitos Biotech , Porto Conte Ricerche, 07041 Alghero, Sardinia, Italy.
authors: Irene
authors: I
authors: Marchesi
authors: Department of Biomedical Sciences, and National Institute of Biostructures and Biosystems, University of Sassari , 07100 Sassari, Sardinia, Italy.
authors: Luca
authors: L
authors: Sanna
authors: Department of Chemistry and Pharmacy, University of Sassari , Via Muroni 23, 07100 Sassari, Sardinia, Italy.
authors: Battistina
authors: B
authors: Asproni
authors: Department of Chemistry and Pharmacy, University of Sassari , Via Muroni 23, 07100 Sassari, Sardinia, Italy.
authors: Gerard A
authors: GA
authors: Pinna
authors: Department of Biomedical Sciences, and National Institute of Biostructures and Biosystems, University of Sassari , 07100 Sassari, Sardinia, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors: Luigi
authors: L
authors: Bagella
authors: Department of Chemistry and Pharmacy, University of Sassari , Via Muroni 23, 07100 Sassari, Sardinia, Italy.
authors: Gabriele
authors: G
authors: Murineddu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole