title: New palbociclib analogues modified at the terminal piperazine ring and their anticancer activities.
abstract: A series of new palbociclib analogs by extensive functionalization of the tail piperazine ring with various carbamates and amides have been synthesized. All the palbociclib derivatives were evaluated for their cytotoxic activities against MCF-7 cell line. From the anti-proliferation activity results, two of the tested compounds (compounds 4d and 4e) showed significant cytotoxic effects. And compounds 4d and 4e exhibited potent anticancer activities in MDA-MB-453 and MDA-MB-231 cells. Among these derivatives compound 4e was found to possess cytotoxicity that is better than standard drug palbociclib. Moreover, compound 4e demonstrated robust tumor growth inhibition in vivo model.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China. Electronic address: wangpeng159seu@hotmail.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jinxin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051361:Cyclin-Dependent Kinase 6 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D011725:Pyridines; D051361:Cyclin-Dependent Kinase 6; C500026:palbociclib
keywords: Anticancer; CDKs; Palbociclib; Synthesis