DNA Alkylating Agents Lapinsky Flashcards
What type of drugs are DNA alkylating agents?
CCNS
How do DNA alkylating agents damage DNA?
alkylation (C,H) of DNA leads to cancer cell apoptosis
DNA alkylating agents are highly reactive ______ compounds
electrophilic
What type of ion is responsible for a partial of full positive charge on DNA alkylating agents?
Aziridinium ion (nitrogen mustards)
What types of compounds do DNA alkylating agents react with?
neutrophilic FGs (nucleic acid bases of DNA)
What is the on target effect of DNA alkylating agents?
Drug forms covalent irreversible bond with DNA
What are the off target effcts of DNA alkylating agents?
- Drug forms covalent bond with protein/enzyme (increases likelihood of long term toxicities)
- Drug forms covalent bond with water/ glutathione (inactive metabolites)
Why do DNA alkylating agents have such a hard time binding to the bases of nucleic acids?
Many nucleophiles in the human body (amino acids, water molecules)
What is the most important nucleophile (desired drug target)?
N7 atom of guanine within cancer cell DNA
Why does Drug-DNA complex result in cancer cell apoptosis?
DNA can no longer unwind to function as a template for DNA replication or translation to mRNA
Why can all DNA alkylating agents potentially cause more cancer?
Alkylated Guanine will base pair with Thymine instead of Cytosine this results in mutation
What can result from DNA mutations by alkylating agents?
- cell apoptosis
- cell senescence
- normal cell –> cancer cell
Why are DNA repair enzymes not as prominent in cancer cell as in normal healthy cells?
cancer cells divide at a rapid, heightened state and tends to induce apoptosis rather than DNA repair
DNA alkylating agents (nitrogen mustards) are ________ the aziridinium ion is the ______ _______
prodrugs; active agent
What drug has L-phenylalanine as the “R” group?
Melphalan
