Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1.

Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1. Research Abstract Details 

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Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1. Abstract Text:

Mireya L McKee,Sean M Kerwin,Mireya L McKee,Sean M Kerwin,

UK-1 is a bis(benzoxazole) natural product displaying activity against a wide range of human cancer cell lines. A simplified analog of UK-1, 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, was previously found to be almost as active as UK-1 against cancer cell lines, and similar to the natural product, formed complexes with a variety of metal ions such as Mg(2+) and Zn(2+). A series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazole analogs of this 'minimal pharmacophore' of UK-1 were prepared. The anti-cancer activity of these analogs was examined in breast and lung cancer cell lines. Spectrophotometric titrations in methanol were carried out in order to assess the ability of UK-1 and these analogs to coordinate with Mg(2+) and Cu(2+) ions. Although none of the new analogs were more cytotoxic than 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, some analogs were identified that display similar cytotoxicity to this simplified UK-1 analog with improved water solubility. UK-1 and all of these new analogs bind Cu(2+) ions better than Mg(2+) ions, and the nature of the 4-substituent is important for the Mg(2+) ion binding ability of these 2-(2'-hydroxyphenyl)benzoxazoles. Previous studies of a limited number of UK-1 analogs demonstrated a correlation between Mg(2+) ion binding ability and cytotoxicity; however, within this series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazoles the variations in cytotoxicity do not correlate with either Mg(2+) or Cu(2+) ion binding ability. These results, together with recent ESI-MS studies of Cu(2+)-mediated DNA binding by UK-1 and analogs, indicate that UK-1 and analogs may exert their cytotoxic effects by interaction with Cu(2+) or other transition metal ions, rather than Mg(2+), and that metal ion-mediated DNA binding, rather than metal ion binding affinity, is important for the cytotoxic effect of these compounds. The potential role of Cu(2+) ions in the cytotoxic action of UK-1 is further supported by the observation that UK-1 in the presence of Cu(2+) displays enhanced cytotoxicity to MCF-7 and A549 cells when compared to UK-1 alone.

Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1. Publishing Authors By Initials

ML McKee,SM Kerwin,ML McKee,SM Kerwin,

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Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry

VOLUME: 16

Page Numbers: 1775-83

Journal Abbreviation: Bioorg. Med. Chem.

ISSN: 1464-3391

DAY: 12

MONTH: 11

YEAR: 2007

Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1. Information

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LANGUAGE: eng

NlmUniqueID: 9413298

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Grant and Affiliation Information for Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1.

AFFILIATION: Department of Chemistry and Biochemistry, Division of Medicinal Chemistry, Institute of Cellular and Molecular Biology, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.

Country: England

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MEDLINETA: Bioorg Med Chem

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