Antiproliferative 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides,a new tubulin inhibitor chemotype |
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Affiliation: | 1. Poznan University of Technology, Institute of Chemical Technology and Engineering, Berdychowo 4, 60-965 Poznan, Poland;2. Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland |
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Abstract: | We discovered a new chemical class of antiproliferative agents, 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides. SAR-guided optimization of the two distinct terminal fragments yielded a compound with 120 nM potency in an antiproliferative assay. Biological activity profile studies (COMPARE analysis) demonstrated that 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides act as tubulin inhibitors, and this conclusion was confirmed via biochemical assays with pure tubulin and demonstration of increased numbers of mitotic cells following treatment of a leukemia cell line. |
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Keywords: | Prostate cancer DU-145 Screening Chemotherapeutic agents Rational single-molecule polypharmacy Tubulin inhibitor |
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