title: Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones.
abstract: A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC(50) values of 4.4 and 5.2microM, respectively, compared to 5-fluorouracil (IC(50)=15.2microM) against MCF-7 cells.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Thirupathi Reddy
authors.forename: P
authors.initials: P
authors.lastname: Narsimha Reddy
authors.forename: Srinivas
authors.initials: S
authors.lastname: Koduru
authors.forename: Chendil
authors.initials: C
authors.lastname: Damodaran
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D048289:Imidazolidines; D007211:Indoles; C514490:imidazolidine-2,4-dione; C015685:aplysinopsin; D014364:Tryptophan
references.citation: Acta Crystallogr Sect E Struct Rep Online. 2008 Oct 18;64(Pt 11):o2122
references.pmid: 21580984
references.citation: BMC Cancer. 2009 Jan 30;9:41
references.pmid: 19183448
references.citation: Cancer Prev Res (Phila). 2009 Mar;2(3):234-43
references.pmid: 19223576
references.citation: Mar Drugs. 2009 May 19;7(2):166-83
references.pmid: 19597579
references.citation: J Med Chem. 2003 Apr 24;46(9):1706-15
references.pmid: 12699388
references.citation: Bioorg Med Chem Lett. 2008 Mar 15;18(6):1784-7
references.pmid: 18308566
references.citation: Bioorg Med Chem Lett. 2010 Jan 15;20(2):600-2
references.pmid: 20005706
references.citation: J Nat Prod. 1994 Jul;57(7):1008-11
references.pmid: 7964781
references.citation: Acta Crystallogr Sect E Struct Rep Online. 2008 Dec 10;65(Pt 1):o62-3
references.pmid: 21581703
references.citation: Bioorg Med Chem Lett. 2007 Dec 15;17(24):6821-4
references.pmid: 17980582
references.citation: Chem Pharm Bull (Tokyo). 2008 Jun;56(6):831-4
references.pmid: 18520089
references.citation: Lloydia. 1977 Sep-Oct;40(5):479-81
references.pmid: 562965