title: Synthesis of unsymmetrical biphenyls as potent cytotoxic agents.
abstract: Twenty-six unsymmetrical biphenyls were synthesized and evaluated for cytotoxic activity against DU145, A549, KB and KB-Vin tumor cell lines. Three compounds 27, 35 and 40 showed very potent activity against the HTCL panel with an IC(50) value range of 0.04-3.23 microM. In addition, fourteen active compounds were all more potent against the drug-resistant KB-Vin cell line than the parental KB cell line. Preliminary SAR analysis indicated that two bulky substituents on the 2,2'-positions of unsymmetrical biphenyl skeleton are necessary and crucial for in vitro anticancer activity, thus providing a good starting point to develop unsymmetrical biphenyls as novel anticancer agents.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: Huan-Fang
authors.initials: HF
authors.lastname: Guo
authors.forename: Kun
authors.initials: K
authors.lastname: Gao
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Liu
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds
references.citation: Life Sci. 2007 Jan 30;80(8):741-8
references.pmid: 17129588
references.citation: J Org Chem. 1997 May 16;62(10):3242-3245
references.pmid: 11671710
references.citation: Cancer Chemother Pharmacol. 2006 Jul;58(1):99-106
references.pmid: 16231181
references.citation: Bioorg Med Chem Lett. 2008 Jan 15;18(2):523-6
references.pmid: 18063366
references.citation: J Nat Prod. 1998 Nov;61(11):1447-51
references.pmid: 9834179
references.citation: J Nat Prod. 2003 Jul;66(7):1022-37
references.pmid: 12880330
references.citation: J Org Chem. 2005 Oct 28;70(22):8932-41
references.pmid: 16238330
references.citation: Bioorg Med Chem. 1997 Aug;5(8):1715-23
references.pmid: 9313872
references.citation: J Nat Prod. 2004 Feb;67(2):273-83
references.pmid: 14987069
references.citation: J Ethnopharmacol. 1999 Oct;67(1):61-8
references.pmid: 10616961
references.citation: Oncology. 1992;49(1):68-71
references.pmid: 1542498
references.citation: J Natl Cancer Inst. 1990 Jul 4;82(13):1113-8
references.pmid: 2359137
references.citation: Drug Discov Today. 2008 Feb;13(3-4):161-71
references.pmid: 18275914
references.citation: Br J Pharmacol. 1994 Nov;113(3):945-53
references.pmid: 7858890
references.citation: Biochem Pharmacol. 2006 Sep 28;72(7):824-37
references.pmid: 16889754
references.citation: J Org Chem. 2002 Mar 22;67(6):1802-15
references.pmid: 11895396