Our previous investigations have demonstrated that members of several classes of organic heterocyclic compounds have potent pharmacological activities as antineoplastic, cytotoxic, hypolipidemic, and antiinflammatory agents. Additional derivatives of several of these classes will be synthesized in order to complete structure activity relationship (SAR) for these classes. Derivatives of several new and/or previously unstudied classes of compounds will also be synthesized. Computer assisted drug design (CADD) will be used as a guide in the selection of derivatives to be prepared. SYBYL 6.3 molecular modeling software with comparative Molecular Field Analysis (SoMFA will be utilized for the CADD studies. The pharmacological activity testing will be performed by Dr. Iris H. Hall at the School of Pharmacy, University of North Carolina at Chapel Hill. In addition to SAR evaluations, mode of action, LD50 values, and pharmacokinetics will be determined on the most potent agents in each chemical class. A series of 3,5-isoxazolidinediones and 3,5-pyrozolidinediones will be synthesized by the condensation of substituted malonyl chlorides and esters with hydroxamic acids, hydroxyl amines, and hydrazine, respectively. The 3,5-pyrozolidinediones will be mono and disubstitued with acylalkyl groups at positions 1 and 2. In a similar manner of series of 1,2,4-triazolidine-3,5-diones will be mono and disubstitued at positions 1 and 2 with acylalkyl groups. Derivatives of 1,5- diazabicyclo[3.1.0]hexane2,4-dione will be synthesized by the reaction of 1-pyrazoline-3,5-diones and acyl substituted dizoalkanes and by the condensation of 1,2 unsubstitued diazridines and malonyl chlorides. Other classes of compounds to be synthesized include 1-alkylideneamino- 2,4azetidinediones, 2-alkylideneaminophthalimides, and other five- membered nitrogen heterocyclic compounds containing one or two ring carbonyl groups
| Grant, Delores J; Hoyo, Cathrine; Oliver, Shannon D et al. (2013) Association of uridine diphosphate-glucuronosyltransferase 2B gene variants with serum glucuronide levels and prostate cancer risk. Genet Test Mol Biomarkers 17:3-9 |
| Vidal, Adriana C; Tucker, Cocoa; Schildkraut, Joellen M et al. (2013) Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study. BMC Cancer 13:556 |
| Pointer, Mildred A; Daumerie, Geraldine; Bridges, LaKessha et al. (2012) Physiological stress increases renal injury in eNOS-knockout mice. Hypertens Res 35:318-24 |
| Vidal, Adriana C; Grant, Delores J; Williams, Christina D et al. (2012) Associations between Intake of Folate, Methionine, and Vitamins B-12, B-6 and Prostate Cancer Risk in American Veterans. J Cancer Epidemiol 2012:957467 |
| Daumerie, Geraldine; Bridges, Lakeesha; Yancey, Sadiqa et al. (2010) The effect of salt on renal damage in eNOS-deficient mice. Hypertens Res 33:170-6 |
| Carney, Skyla T; Lloyd, Michael L; MacKinnon, Shanta E et al. (2009) Cannabinoid regulation of nitric oxide synthase I (nNOS) in neuronal cells. J Neuroimmune Pharmacol 4:338-49 |
| Gerald, Tonya M; Howlett, Allyn C; Ward, Gregg R et al. (2008) Gene expression of opioid and dopamine systems in mouse striatum: effects of CB1 receptors, age and sex. Psychopharmacology (Berl) 198:497-508 |
| Jones, Jenelle D; Carney, Skyla T; Vrana, Kent E et al. (2008) Cannabinoid receptor-mediated translocation of NO-sensitive guanylyl cyclase and production of cyclic GMP in neuronal cells. Neuropharmacology 54:23-30 |
| Howlett, Allyn C; Mukhopadhyay, Somnath; Norford, Derek C (2006) Endocannabinoids and reactive nitrogen and oxygen species in neuropathologies. J Neuroimmune Pharmacol 1:305-16 |
| Wilson 3rd, Willie; Pardo-Manuel de Villena, Fernando; Lyn-Cook, Beverly D et al. (2004) Characterization of a common deletion polymorphism of the UGT2B17 gene linked to UGT2B15. Genomics 84:707-14 |
