Browsing by Author "Mabank, Tanya"
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- ItemSynthesis of 2-substituted tetrahydroisoquinolin-6-ols: potential scaffolds for estrogen receptor modulation and / or microtubule degradation(ARKAT USA, 2019) Mabank, Tanya; Alexandre, Kabamba B.; Pelly, Stephen C.; Green, Ivan R.; Van Otterlo, Willem A. L.ENGLISH ABSTRACT: 6-Methoxytetrahydroisoquinoline hydrochloride was converted into four small libraries of substituted ureas, thioureas, sulfonamides and N-aryls, using the tetrahydroisoquinoline nitrogen as the scaffold-linking atom. Some of the compounds were evaluated for their ability to inhibit cell proliferation using the MCF7 (invasive ductal carcinoma) cell line.
- ItemSynthesis of novel Tetrahydroisoquinoline-related estrogen receptor modulators(Stellenbosch : Stellenbosch University, 2019-03) Mabank, Tanya; Van Otterlo, Willem A. L.; Pelly, Stephen C.; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.ENGLISH ABSTRACT: The tetrahydroisoquinoline (THIQ) core has displayed a rich history as a biologically active natural product and is an interesting scaffold to use in drug discovery. Its structural skeleton is present in a number of structurally diverse natural products exhibiting a wide range of biological, pharmaceutical and estrogen receptor (ER) activities.1-5 Estrogen is a steroid hormone which influences the functioning of many target tissues. However, the normal existence of estradiol in women affected with breast cancer may worsen the infection; and a deficiency may increase the risk of various hormone related diseases. Estradiol is the natural ligand responsible for modulating the expression and/or repression of specific estrogen gene transcriptions.6,7 In this project, we therefore considered the synthesis of four small sets of THIQ-based compounds with the potential ability to bind the ER with affinities competing with that of estradiol. The THIQ compounds generated included structures with or without linker groups, and a lactam core without a linker group. The compounds were structurally designed by making use of Schrodinger and Acclerys Discovery Studio software, to accommodate the receptors binding pocket and improve the potency and selectivity toward the ERβ. With the successful synthesis of the THIQ compounds generated, which included structures with or without linker groups, and a lactam core without a linker group, further biochemical studies were explored. During the synthesis of these final compounds, it was found that once demethylated, the final compounds showed some degree of decomposition and sedimentation upon preparation for bioevaluations. Whole cell testing however, only revealed that only one compound showed potential activity, with the rest showing quite poor activity. In terms of the cell proliferation, this compound (65%) compared well to the medicinal agent, Fulvestrant, which slowed growth to 63.5%.