Theoretical studies of the reactivity of model systems for the pharmacophores of the anthracycline family of drugs will be undertaken using semiempirical formalisms. (AM1, AM1-SM1/SM2, ETC). The thrust of these studies is to gain insight from quantum chemistry/pharmacology, molecular modeling and statistical inference to understand molecular- level features that govern chemical reactivity but are concealed by the molecular structure and raw experimental data. Electronic properties (absolute electronegativity and hardness; HOMO, LUMO and SOMO orbital energies; enthalpy of reaction for electron attachment; free energies of solvation, etc.) of some 16 and 42 derivatives of naphthaquinone and anthraquinone, respectively, will be calculated and used as variables for the purpose of correlating the variables with experimental one- and two- electron reduction potentials. The electronic properties will also be correlated with antitumor activity (ED25) and acute toxicity (LD50) for those cases where such data are available. Simulated annealing techniques will be used to study the relative stabilities of conformers/rotamers, keto-enol forms and radicals. Solvation free energies will be calculated to determine their (or, in combination with other electronic properties) possible correlations with reduction potentials, antitumor activity (ED25) and acute toxicity (LD50). The studies will be used to develop structure/activity relationships which will, in turn, be used to predict the biological activities of theoretical models - not yet-synthesized-drugs.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Clark Atlanta University
United States
Zip Code
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