Anti-cancer Agents

Antimetabolites

Alkylating Agents

Cytotoxic Antibiotics

Plant alkaloids/microtubule inhibitors

Folate antagonists

Nucleic acid synthesis inhibitors

Nitrogen mustards

Nitrosoureas

Form covalent bond with DNA which then inhibits DNA synthesis during S phase. They form irreversible bonds on guanine residues on the same or adjacent strands. Intra and inter chain linking occurs and during replication some parts of the DNA is unpaired making it more susceptible to alkylation.

Antracyclines

Taxanes

Vinca alkaoids

General MOA: Acts by competition, block or subvert metabolic pathways in the biosynthesis of DNA

Folate metabolism- Required for the synthesis of purine nucleotides and thymidylate which are essential for DNA synthesis and cell division. FOLATE--> DHF-->THF--> CH2THF-->CH3THF--> Purine Biosynthesis

Antagonist is structurally similar

METHOTREXATE- Inhibits the metabolism of folates by inhibiting the action of Dihydrofolate Reductase which converts folate to THF. Maximal effects are S-phase specific (specific to the synthesis phase)

Purine analogues: 6-thioguanine, 6-mercaptopurine

Pyrimidine analogues: 5-fluorouracil, capecitabine, cytarabine

Inhibits enzymes either directly or after formation of a further false compound, form a false RNA or DNA which is unable or slower to replicate due to extra binding groups

5-fluorouracil exerts anti-cancer effects by inhibiting thymidylate synthase and incorporation of metabolites into RNA and DNA. It is metabolised in the gut and the liver. CAPECITABINE is a prodrug (for oral administration) which is activated by cascade of 3 enzymes for 5-FU

They are flat molecules which interpose themselves between the coils of DNA strands and cause inhibition of macromolecular biosynthesis

Substances which have microbial origin which prevents mammalian cell division.

DOXORUBICIN- Interacts with DNA by intercalation and prevents correct uncoiling and exposure of DNA by stabilising DNA-topoisomerase complex 2. Used to treat leukaemias, lymphomas and solid tumours. Adverse effects: cardiac toxicity- produces oxygen radical which are normally inactivated by catalase and glutathione peroxidase

Acts on tubulin and microtubule dynamics and is of plant origin

Spindle poisons: VINCRISTINE and VINBLASTINE

Binds to tubulin and inhibits the polymerisation into microtubules. Prevents spindle formation and causes arrest at the stage of metaphase

E.g- PACLITAXEL (TAXOL) and DOCETAXEL

Interferes with mitosis by promoting the formation of intracellular microtubules and preventing disassembly of the formed microtubules during anaphase

Derivatives of mustard gas which forms bifunctional DNA adducts. The prodrugs are activated in the liver by Cytochrome P450 enzymes. E.g- CYCLOPHOSPHAMIDE and IFOSFAMIDE

E.g- CARMUSTINE

Folinic Acid is used with a high dose of MTX as a form of rescue for the highly proliferating cells of the bone marrow and GI mucosa

Alkylation of DNA and forms carbamoyl adducts with proteins. Can also pass through the BBB so it can be used for the treatment of brain tumours, myelomas and Hodgkin's lymphoma

Alkylating like

E.g-CISPLATIN

Platinum complexes react and bind which causes the cross-linking of DNA--> apoptosis.