Design, Synthesis and Biological Evaluation of Novel Estradiol-Triazole Analogs Targeting Epidermal Growth Factor Receptors in Colorectal Cancer

Author

Faez Alotaibi, South Dakota State UniversityFollow

Document Type

Thesis - Open Access

Award Date

2017

Degree Name

Master of Science (MS)

Department / School

Chemistry and Biochemistry

First Advisor

Fathi T. Halaweish

Keywords

click chemistry, colerectal cancer, docking, EGFR, estradiols, triazole

Abstract

Colorectal cancer is a life threatening and second cause of death from cancer in the United States. Several proteins (molecular targets) are highly expressed in Colorectal cancer (CRC). Among these molecular targets is Epidermal Growth Factor Receptors (EGFRs) which are overexpressed in cancer cells. Targeting and blocking the downstream signaling could lead to cease cell proliferation and division and hence control the spread of the disease. Molecular modeling is a powerful tool in drug discovery, which has been utilized to design many drug candidates that exhibit biological effect in many disease including cancer. Additionally, pharmacophores such as 1,2,3-triazole showed potency towards many diseases including cancer. Therefore, incorporation of 1,2,3-triazole on a carrier such as estradiol could lead to novel analogs in drug discovery for treatment of cancer. A library of 800 compound containing 1,2,3-triazole-estradiol analogs were designed and virtually screened with seven molecular targets belong to EGFRs utilizing OpenEye® software. Among the designed candidates, fourteen of estradiol-triazole analogs were synthesized and biologically evaluated. Antiproliferation/cytotoxicity assay conducted on CRC cancer cell line (HT-29) showed that 5 out 14 analogs demonstrated potential antiproliferation activities ranging from 3.5 μM to 30 μM in comparison to a chemotherapeutic agent 5- flurouracil (5-FU) (IC50 17.3 μM) which is a standard drug for CRC.

Library of Congress Subject Headings

Epidermal growth factor -- Receptors.
Cancer cells -- Growth -- Regulation.
Colon (Anatomy) -- Cancer.
Rectum -- Cancer.
Estradiol.
Triazoles.

Description

Includes bibliographical references

Format

application/pdf

Number of Pages

147

Publisher

South Dakota State University

Recommended Citation

Alotaibi, Faez, "Design, Synthesis and Biological Evaluation of Novel Estradiol-Triazole Analogs Targeting Epidermal Growth Factor Receptors in Colorectal Cancer" (2017). Electronic Theses and Dissertations. 1189.
https://openprairie.sdstate.edu/etd/1189