Abstract

This proposal describes the preparation of new molecules that hold promise as DNA cleaving agents. All the molecules being proposed possess one common feature, they contain a [3]cumulene moiety along with an array of conjugated double and triple bonds. Cumulenes have been postulated as reactive intermediates in the triggering mechanism of Neocarzinostatin chromophore (and analogs), one of the most potent naturally occurring DNA cleaving agent known. The work being proposed is an attempt to put to practical use a new process discovered in these laboratories, the preparation of functionalized [3]cumulenes. The new reaction was proposed in a previous NIH-MBRS proposal and consists of a Lewis acid induced rearrangement/dehydration of epoxy alkynols to [3]cumulenes and hydroxy allenes. This reaction will be exploited for the synthesis of several [3]cumulenes possessing the structural features capable of undergoing Bergman/Meyers type cycloaromatization to afford diradical intermediates (the species responsible for DNA cleaving activity). After the proposed molecules have been synthesized, provisions have been made to test out the effectiveness as DNA cleaving agents via gel electrophoresis techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM008247-11
Application #
6107412
Study Section
Project Start
1998-02-01
Project End
1999-01-31
Budget Start
Budget End
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Clark Atlanta University
Department
Type
DUNS #
065325177
City
Atlanta
State
GA
Country
United States
Zip Code
30314

  Publications

Ifere, Godwin O; Equan, Anita; Gordon, Kereen et al. (2010) Cholesterol and phytosterols differentially regulate the expression of caveolin 1 and a downstream prostate cell growth-suppressor gene. Cancer Epidemiol 34:461-71
Mariam, Yitbarek H; Musin, Ryza N (2008) Transition from moderate to strong hydrogen bonds: its identification and physical bases in the case of O-H...O intramolecular hydrogen bonds. J Phys Chem A 112:134-45
Kimbro, K Sean; Duschene, Kaitlin; Willard, Margeret et al. (2008) A novel gene STYK1/NOK is upregulated in estrogen receptor-alpha negative estrogen receptor-beta positive breast cancer cells following estrogen treatment. Mol Biol Rep 35:23-7
Chu, Qinghui; Pang, Yi (2004) Vibronic structures in the electronic spectra of oligo(phenylene ethynylene): effect of m-phenylene to the optical properties of poly(m-phenylene ethynylene). Spectrochim Acta A Mol Biomol Spectrosc 60:1459-67
Sannigrahi, Biswajit; McGeady, Paul; Khan, Ishrat M (2004) Helical poly(3-methyl-4-vinylpyridine)/amino acid complexes: preparation, characterization, and biocompatibility. Macromol Biosci 4:999-1007
Liang, Sidney; Bu, Xiu R (2002) Tertiary pentyl groups enhance salen titanium catalyst for highly enantioselective trimethylsilylcyanation of aldehydes. J Org Chem 67:2702-4
Vanderveer, Donald; Colon, Marisabel Lebron; Bu, Xiu R (2002) Crystal structure of a chiral Ni complex: (R,R)-N,N'-bis(3-t-butylsalicylidene)-1,2-cyclohexanediaminonickel(II). Anal Sci 18:1283-4
Musey, Paul I; Ibim, Sobrasua M; Talukder, Niranjan K (2002) Development of artificial blood vessels: seeding and proliferation characteristics of endothelial and smooth muscle cells on biodegradable membranes. Ann N Y Acad Sci 961:279-83
Chiang, C F; Okou, D T; Griffin, T B et al. (2001) Green fluorescent protein rendered susceptible to proteolysis: positions for protease-sensitive insertions. Arch Biochem Biophys 394:229-35
Johnson, K P; Rowe, G C; Jackson, B A et al. (2001) Novel antineoplastic isochalcones inhibit the expression of cyclooxygenase 1,2 and EGF in human prostate cancer cell line LNCaP. Cell Mol Biol (Noisy-le-grand) 47:1039-45

Showing the most recent 10 out of 17 publications