- Collection:
- Atlanta University and Clark Atlanta University Theses and Dissertations
- Title:
- The design, synthesis, characterization and biological screening evaluation of 1-adamantyl chalcones as potentianal breast cancer agents, 1999
- Creator:
- Kaimari, Tawfeq
- Date of Original:
- 1999-02-01
- Subject:
- Degrees, Academic
Dissertations, Academic - Location:
- United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
- Medium:
- theses
dissertations - Type:
- Text
- Format:
- application/pdf
- Description:
- The main objective of this research is to develop and identify a novel class of compounds that can be used to treat metastatic breast cancer. To our knowledge no study concerning the anti-breast cancer activity of chalcone and chalcone-like derivatives containing the adamantyl moiety has been reported in the current available literature. This thesis contains the first reported study specifically focused on the activity of chalcone and chalcone-like derivatives containing the adamantyl moiety against breast cancers. Many chalcone, flavanone and isoflavanone derivatives are known to exhibit antiproliferative effects against breast cancer cells and display binding affinities for the ER. Adamantane shows abroad spectrum of biological activity and its addition to organic compounds can enhance their biological activity. A total of twenty four adamantyl chalcone and chalcone-like compounds were synthesized and characterized. These compounds were conveniently divided into four categories: 1) Senes I. Chalcone-like compounds with the aromatic A ring replaced by the adamantane moiety; 2) Series II. Chalcone-like compounds with modification in the A ring and B region; 3) Series III. Chalcone-like compounds with the aromatic C ring replaced by heterocyclic group; and 4) Series IV. Chalcone with the adamantane moiety substituted on the aromatic A ring. The Aldol condensation method was used as a convenient way to modify the chalcone structure. Iron filings were used as a catalyst in a new synthetic method for the adamantylation of benzene derivatives. This new method provided for easy separation and afforded high percent yield of product. These compounds were characterized by melting point, elemental analysis, GC-MS, FT-IR, FT-NMR, and X-ray. Selected compounds from each series were then tested for biological activity in breast cancer derived cell lines MCF-7 (ER-positive), MDA-MB435 (ER-negative) and a control breast cancer cell line (MCF-10). One compound from series I and five compounds from series III were effective in prohibiting cell growth in the selected cancer cell lines but not in the control cell line. The lethal concentration at 50% (LC50) values in MCF-7 range from 5 X 10'3 M to 5 X 10'5 M and in MDA-MB435, the LC50 values range from 1 X I0'3 to 5 X 10'6. The control cell line showed no significant decrease in cell viability in the presence of these compounds. The ability of the parent compound 47a to reduce the sensitivity of the cell lines towards epidermal growth factor (EGF) and transforming growth factor-a (TGF-a) were tested. Compound 47a in MCF-7 cell line reversed stimulatory effect of EGF but the stimulatory effect of TGF-a was reversed in MDA-MB435 cell line. Some of the newly synthesized compounds showed greater activity than currently used drugs such as tamoxifen, genestein and doxyrubicin.
Degree type: dissertation
Degree name: Doctor of Philosophy (PhD)
Granting institution: Clark Atlanta University
Department: Department of Chemistry - Metadata URL:
- http://hdl.handle.net/20.500.12322/cau.td:1999_kaimari_tawfeq
- Holding Institution:
- Atlanta University Center Robert W. Woodruff Library
- Rights:
-
