title: Synthesis and antitumor activity of novel 3,4-diaryl squaric acid analogs.
abstract: A series of novel 3,4-diaryl squaric acid analogs 4a-r related to combretastatin A-4 (CA4) using squaric acid as the cis-restricted linker were prepared and studied for their anticancer activity against selected human cancer cell lines. New compounds 4g, 4k, 4m, 4n, 4p, 4q and 4r exhibit strong activities against human leukemia cells with IC50 values of ≤20 nM and compounds 4k, 4n, 4p, 4q and 4r showed potent activities against a panel of human tumor cell lines. Compounds 4n and 4p arrest tumor cell cycle in G2-M phase. Computational modeling analysis suggests that the binding mechanism of compound 4n to the colchicine binding site on the microtubules is similar to that of CA4.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People's Republic of China.
authors.forename: Zong-Ying
authors.initials: ZY
authors.lastname: Liu
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Yan-Xing
authors.initials: YX
authors.lastname: Han
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Zhuo-Rong
authors.initials: ZR
authors.lastname: Li
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003503:Cyclobutanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003503:Cyclobutanes; C030042:squaric acid
keywords: 3,4-Diaryl squaric acid analogs; Anticancer; Cytotoxic agents