title: Synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as anticancer agents.
abstract: A new library of small molecules with structural features resembling combretastatin analogs was synthesized and evaluated for anticancer activity against a panel of 60 human cancer cell lines. Three novel acrylonitrile analogs (5, 6and13) caused a significant reduction in cell growth in almost all the cell lines examined, with GI50values generally in the range 10-100 nM. Based on the structural characteristics of similar drugs, we hypothesized that the cytotoxic activity was likely due to interaction with tubulin. Furthermore, these compounds appeared to overcome cell-associated P-glycoprotein (P-gp)-mediated resistance, since they were equipotent in inhibiting OVCAR8 and NCI/ADR-Res cell growth. Given that antitubulin drugs are among the most effective agents for the treatment of advanced prostate cancer we sought to validate the results from the 60 cell panel by studying the representative analog6utilizing prostate cancer cell lines, as well as exploring the molecular mechanism of the cytotoxic action of this analog.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors: Narsimha Reddy
authors: NR
authors: Penthala
authors: Vijayakumar N
authors: VN
authors: Sonar
authors: Jamie
authors: J
authors: Horn
authors: Markos
authors: M
authors: Leggas
authors: Jai Shankar K B
authors: JS
authors: Yadlapalli
authors: Peter A
authors: PA
authors: Crooks
references: Curr Opin Pharmacol. 2001 Aug;1(4):370-7
references: 11710735
references: Proc Natl Acad Sci U S A. 1980 Mar;77(3):1561-5
references: 6103535
references: Cancer Res. 2006 Jan 15;66(2):951-9
references: 16424030
references: Drug Resist Updat. 2001 Dec;4(6):392-401
references: 12030786
references: Eur J Med Chem. 2012 Jun;52:22-32
references: 22449653
references: J Med Chem. 1998 Jul 30;41(16):3022-32
references: 9685242
references: Anticancer Drug Des. 1998 Dec;13(8):981-93
references: 10335271
references: J Med Chem. 2003 Feb 13;46(4):525-31
references: 12570374
references: J Med Chem. 2006 Jun 1;49(11):3033-44
references: 16722619
references: Acta Crystallogr C. 2007 Dec;63(Pt 12):o743-5
references: 18057629
references: Cancer Res. 1992 Jul 15;52(14):3892-900
references: 1617665
references: Org Biomol Chem. 2003 Sep 7;1(17):3033-7
references: 14518125
references: Org Biomol Chem. 2005 Apr 21;3(8):1534-40
references: 15827653
references: J Med Chem. 1991 Aug;34(8):2579-88
references: 1875350
references: J Med Chem. 2004 Jun 17;47(13):3438-49
references: 15189040
references: Bioorg Med Chem. 2012 Jan 15;20(2):903-9
references: 22192936
references: Mol Pharmacol. 1988 Aug;34(2):200-8
references: 3412321
references: Med Res Rev. 1998 Jul;18(4):259-96
references: 9664292