Persistent organochlorines (OCs) bioaccumulate in aquatic biota and potentially impair reproduction via endocrine disruption. The present research evaluated estrogenic effects of the OCs, chlordecone (CD) and o,p'-DDT/DDE, and the antiestrogenicity of 3,4,5,3',4',5'-hexachlorobiphenyl (345-HCB) in juvenile rainbow trout, utilizing vitellogenesis as a biomarker. Vitellogenesis, estrogen regulated hepatic production of the yolk...
Recent developments in NMR hardware have extended the reach of natural products chemists to structure elucidation of compounds isolated on a nanomolar scale. In parallel with advances in hardware new NMR techniques for structure elucidation have evolved, e.g. quantitative NOEs, residual dipolar couplings (RDCs)and diffusion-ordered spectroscopy (DOSY). The application of...
A Diels-Alder approach to biaryls (DAB) has been applied towards the synthesis
of highly substituted, programmable biaryl templates. Tri- and tetra-ortho-substituted
biaryls can be produced in just three to four steps from commercially available materials
utilizing the Diels-Alder [4+2] cycloaddition. The methods described herein will
illustrate the ability of mono...
Ambifunctional axially chiral 2,2',6,6'-tetrasubstituted biphenyls containing nucleophilic (or basic) functional groups juxtaposed with hydrogen-bond donors were synthesized and their properties studied. Applications for the prepared biaryls as potential organocatalysts for enantioselective carbon-carbon bond forming reactions were examined. Processes investigated included: aldol, Michael, nitroaldol (Henry), and Baylis-Hillman reactions.
The novel amidoamine...
Aerobic organisms have evolved many sensory mechanisms that allow
response to oxidants in the environment. One area of interest is the relationship
between the activity of the tumor suppressor protein p53 and the redox state of
thioredoxin. Human p53 activity is severely compromised in budding yeast lacking
thioredoxin reductase. Evidence...
Overtly non-toxic doses of organochlorine (OC) insecticides perturb lipid homeostasis
in mice and rats. To increase understanding of how chlordecone (CD), an OC
insecticide, modulates cholesterol (CH) homeostasis, we determined the effect of CD
pretreatment on the tissue and hepatic subcellular distribution of exogenous [¹⁴C]CH. Corn oil alone or CD...
I have participated in a drug discovery program designed to screen marine algae for
inhibitors of cancer-related enzymes, antitumor compounds, antiinflammatory substances,
and other agents of potential pharmaceutical utility. Over 1,500 lipid and aqueous extracts
of marine plants and animals were surveyed for biomedical potential. Assays designed to
screen extracts...
The isoprenoid pathway is one of the major biosynthetic pathways of secondary metabolites. Isoprenoids with a C₂₀ skeleton are known as diterpenoids and are derived from the common precursor, geranylgeranyl diphosphate (GGPP). This dissertation describes approaches to discover the diterpene synthase enzymes which provide the backbone structures for pleuromutilin and...
This project describes the investigation of marine cyanobacteria collected from the Red Sea with an emphasis on the identification and prioritization of biologically active fractions for future purification and molecular structure elucidation of medicinally relevant secondary metabolites.
Five crude extracts of taxonomically unidentified Red Sea cyanobacteria supplied by Egyptian collaborators...