ASU Electronic Theses and Dissertations
- 2 English
A potential new class of cancer chemotherapeutic agents has been synthesized by varying the 2 position of a benzimidazole based extended amidine. Compounds 6-amino-2-chloromethyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1A) and 6-amino-2-hydroxypropyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1B) were assayed at the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP) and found to be cytotoxic at sub-micromolar concentrations, and have shown between a 100 and a 1000-fold increase in specificity towards lung, colon, CNS, and melanoma cell lines. These ATP mimics have been found to correlate with sequestosome 1 (SQSTM1), a protein implicated in drug resistance and cell survival in various cancer cell lines. Using the DTP COMPARE algorithm, compounds …
- Darzi, Evan Rashied, Skibo, Edward, Gould, Ian, et al.
- Created Date
Changes to a cell's DNA can result in cancer, which is permanently sustained cellular proliferation. When malfunctioning genes, oncogenes, were verified to be of human origin in the 1970s, drugs were designed to target their encoded, abnormal enzymes. Tyrosine kinases have been established as an oft-modified oncogene enzyme family, but the protein tyrosine phosphatases (PTPs) were not investigated as thoroughly. PTPs have gradually been established as relevant enzymes that work in tandem with tyrosine kinases in cell signaling and are not just "house-keeping" enzymes. Some PTPs are thought to initiate tumorigenesis, and others may play a complementary role after the …
- Fadgen, Casey, Rose, Seth D, Francisco, Wilson, et al.
- Created Date