Oncology: DNA Alkylating Agents Lapinsky Flashcards
What are DNA Alkylating agents classified as?
CCNS drugs
DNA alkylating agents are capable of introducing alkyl groups onto what sites within biological macromolecules?
Nucleophilic
DNA alkylating agents tend to work according to the…
Rate therapy of cancer chemotherapy
What are cancer cells more sensitive to?
DNA damage via alkylation of DNA
DNA alkylating agents as anti-cancer drugs are
Highly reactive
What ion do DNA Alkylating contain that has a partial of a full positive charge? Which agents have this ion?
Aziridinium ion; Nitrogen Mustards
What kind of compounds are DNA alkylating agents?
Electrophiles
DNA alkylating agents contain a good ________. What ion is it?
Leaving group; Cl-
What is the desired target of the DNA alkylating agents?
DNA
What are undesired targets of DNA alkylating agents?
Protein and enzymes
What happens if DNA alkylating agents bind to their undesired drug targets?
More likely to have long lasting ADRs
What is the single most important nucleophile for the alkylating agents to bind to?
The N7 atom of guanine
What 2 things can cause the alkylating agents to have some the worst long lasting adverse side effects?
- Formation of covalent, irreversible drug
- Lack of drug target and cell selectivity
ALL DNA alkylating agents are potentially what 2 things?
Mutagenic and carcinogenic
The shift from KETO tautomer of guanine to the ENOL tautomer of alkylated Guanine leads alkylated guanine to do what?
Abnormally base pair with thymine instead of cytosine
DNA mutations resulting from the alkylation of DNA by a DNA alkylating agent could potentially lead to what 3 things?
- Cell apoptosis
- An irreversible state of cell dormancy
- Conversion of a normal healthy cell into a cancer cell
What is it called when a cell goes into irreversible dormancy?
Cell senescence
Alkylated DNA within cancer cells acts as a ________ to induce cell apoptosis
Chemical signal
What functional group mimics a purine for DNA and RNA synthesis in Bendamustine?
Benzimidazole ring
What is the natural amino acid in Melphalan?
L- phenylalanine
What are the 2 nitrogen mustards?
- Melphalan
- Bendamustine
Since cancer cells spend less time in the resting phases than normal cells, cancer cells are more likely to be?
More metabolically active
Original prototype nitrogen mustard
Mechlorethamine
When cancer cells are tricked into taking up the DNA alkylating agents more than the normal cells
Preferential killing
