chemotherapy mechanism of action

• Competitively inhibits DHFR preventing FH4 formation
• G1/S

Bypasses blocked reductase enzyme --> replenish folate pool

• 5-FUTP - block RNA processing
• 5-FdUMP --> inhibit thymidylate synthase --> inhibit DNA synthesis
• G1/S

• converted to 5-FU
• 5-FdUMP --> inhibit thymidylate synthase --> inhibits DNA synthesis

• converted to 5-FU
• inhibit thymidylate synthase --> inhibit DNA synthesis

• phosphorylated --> araCTP --> decrease DNA synthesis
• competitive inhibitor --> DNA polymerase --> inhibits chain elongation and ligation
• S

• diphosphate --> inhibits ribonucleotide reductase --> inhibit DNA synthesis
• triphosphate --> inhibits DNA polymerases --> arrests DNA synthesis and induces apoptosis

• substrates for HGPRT + SAM + TPMT --> methylation (inhibition of purine synthesis)
• blocks formation of AMP
• non-functional RNA and DNA

dephosphorylated --> phosphorylated --> triphosphate --> inhibits DNA polymerase and ribonucleotide reductase --> decrease DNA synthesis

phosphorylated --> incorporated into DNA --> interfere with DNA repair.

• inhibits ribonucleotide reductase --> inhibit DNA synthesis
• G1/S

• blocks ability of tubulin to polymerize --> prevent assembly
• M

• bind to already formed spindles --> prevent dissembly
• M

• DNA intercalation
• ROS
• Topoisomerase II inhibition
• S phase

• intercalates between G-C
• inhibit RNA polymerase
• M

• DNA intercalation
• hydroxyl free radicals formation

topoisomerase II inhibition

topoisomerase I inhibition

• more acidic G
• destabilize G
• bi-functional agent

hydroxylation --> acrolein + phosphoramide mustard

Hydrolysis --> acrolein + ifosfamide mustard

DNA cross-links

oxidation --> diazomethane --> guanine methylation

N-demethylation --> MTIC --> methylcarbonium --> guanine methyl alkylation

desulfuration --> TEPA

Lose Cl and forms cross-links