Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model |
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| Authors: | Youri Oh Hoyong Jung Hyejin Kim Jihyun Baek Joonhong Jun Hyunwook Cho Daseul Im Jung-Mi Hah |
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| Affiliation: | College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea; (Y.O.); (H.J.); (H.K.); (J.B.); (J.J.); (H.C.); (D.I.) |
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| Abstract: | Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Given the hybridized 3D-QSAR models, we designed and synthesized 4-benzyloxy-1-(2-arylaminopyridin-4-yl)-1H-pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity. |
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| Keywords: | polo-like kinase 1 (PLK1) pyrazole quantitative structure-activity relationship hybridization |
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