title: Synthesis and anticancer activities of ceritinib analogs modified in the terminal piperidine ring.
abstract: A series of new ceritinib analogs by extensive functionalization of the tail piperidine ring with various phosphamides and carbamates have been synthesized. All the ceritinib derivatives were evaluated for their cytotoxic activities against H2228 cell line. From the activity profile obtained, three of the tested compounds (compounds 4, 7 and 9) showed significant cytotoxic effects. Among these derivatives compound 9 was found to possess cytotoxicity that is better than standard drug ceritinib (IC50 = 24 nM). Moreover, compound 9 demonstrated robust tumor growth inhibition in vivo model.
authors: Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China; School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address: wangpeng159seu@hotmail.com.
authors: Peng
authors: P
authors: Wang
authors: School of Chemistry & Chemical Engineering, Southeast University, Nanjing 210096, China.
authors: Jin
authors: J
authors: Cai
authors: School of Chemistry & Chemical Engineering, Southeast University, Nanjing 210096, China.
authors: Junqing
authors: J
authors: Chen
authors: School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address: jimin@seu.edu.cn.
authors: Min
authors: M
authors: Ji
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D008297:Male; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D013450:Sulfones; C586847:ceritinib
keywords: ALK; Anticancer; Ceritinib analogs; Synthesis