Dominican University of California
 

Oral Presentations - Guzman 306

Presentation or Panel Title

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

Department

Natural Sciences and Mathematics

Student Type

Undergraduate

Faculty Mentor

Maria Graciela Carranza

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.

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Apr 24th, 1:40 PM Apr 24th, 1:55 PM

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.