Oral Presentations - Guzman 306
Synthesis of Novel Tyrosine Derivatives of Temozolomide and Their Biological Evaluation Against Breast Cancer Cells
Location
Guzman 306
Start Date
4-24-2015 1:40 PM
End Date
4-24-2015 1:55 PM
Student Type
Undergraduate
Faculty Mentor(s)
Maria Graciela Carranza, Ph.D.
Presentation Format
Oral Presentation
Abstract/Description
Breast cancer is the second leading cause of death in females, effecting one in eight women. Temozolomide (TMZ) is an alkylating agent that inhibits cellular reproduction and causes apoptosis of the cells. It has demonstrated activity against glioma and melanoma, as well as preclinical activity against breast cancer. The main focus of this research is the synthesis of L- and D-tyrosine derivatives of TMZ and their effects in breast cancer cells. It has been shown that tyrosine can act as a ligand potentially targeting nuclear hormone receptors. Thus, tyrosine may be capable “directing” TMZ to breast cancer tissue. We proposed that by combining L- and D-tyrosine methyl ester hydrochloride with TMZ into a single molecule, directly or via linkers, will create a more effective anti-cancer drug than the TMZ parent drug. The novel derivatives were synthesized in good yields and their anticancer efficacy was evaluated over several hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. Results show that at a concentration of 2 x 10-5M compounds 1, 2 and 3 display 32%, 38% and 34% greater in vitro growth inhibitory activity when compared to TMZ in hormone-dependent T47D breast cancer cell line. Structure activity relationship (SAR) analysis suggests the influence of both the length of the linker (0, 1 and 3 carbons) and the stereochemistry of the tyrosine adduct (L- versus D-) on the anticancer activity of the derivatives. Further studies will be undertaken to evaluate the effectiveness of this family of compounds.
Synthesis of Novel Tyrosine Derivatives of Temozolomide and Their Biological Evaluation Against Breast Cancer Cells
Guzman 306
Breast cancer is the second leading cause of death in females, effecting one in eight women. Temozolomide (TMZ) is an alkylating agent that inhibits cellular reproduction and causes apoptosis of the cells. It has demonstrated activity against glioma and melanoma, as well as preclinical activity against breast cancer. The main focus of this research is the synthesis of L- and D-tyrosine derivatives of TMZ and their effects in breast cancer cells. It has been shown that tyrosine can act as a ligand potentially targeting nuclear hormone receptors. Thus, tyrosine may be capable “directing” TMZ to breast cancer tissue. We proposed that by combining L- and D-tyrosine methyl ester hydrochloride with TMZ into a single molecule, directly or via linkers, will create a more effective anti-cancer drug than the TMZ parent drug. The novel derivatives were synthesized in good yields and their anticancer efficacy was evaluated over several hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. Results show that at a concentration of 2 x 10-5M compounds 1, 2 and 3 display 32%, 38% and 34% greater in vitro growth inhibitory activity when compared to TMZ in hormone-dependent T47D breast cancer cell line. Structure activity relationship (SAR) analysis suggests the influence of both the length of the linker (0, 1 and 3 carbons) and the stereochemistry of the tyrosine adduct (L- versus D-) on the anticancer activity of the derivatives. Further studies will be undertaken to evaluate the effectiveness of this family of compounds.