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• Chemotherapy mechanisms –

  Topoisomerase inhibitors – prevent DNA uncoiling

  Microtubule inhibitors – prevents mitosis

  Alkylating agents – damages DNA and forms breaks in strands. DNA replication stops.

  Antimetabolites – block nucleotide formation for DNA replication

  Monoclonal antibodies – recognises overexpressed antigens.
• Intercalating agents – disrupts DNA structure as the agents have planar rings that can fit between DNA bases.
• Intercalating agents – disrupts DNA structures as it fits between DNA bases due to their planar ring structure. They interfere with enzymes needed for replication and transcription.

  Anthracyclines is anticancer properties. Intercalates between bases and disrupts DNA structure and processes for cancer growth.
• Doxorubicin – is an anthracycline. Inserts itself between DNA during replication. The interference leads to DNA strands cut as it disrupts activity of DNA topoisomerase II. This prevents DNA replication and stops cell division leading to cell death.
• Doxorubicin – acts as DNA topoisomerase II poison. Stabilizes complex formed between DNA and topoisomerase II.

  Apoptosis triggered due to a lot of DNA enzyme stabilized complexes.
• DNA bound doxorubicin – buckle caused due to insertion at GC and CG bases. Buckle disrupts DNA structure by interfering with the van der waal forces.

  Distortion stabilized by electrostatic interactions, hydrogen bonding and aromatic pi-pi interactions.
• DNA bound Dactinomycin – interacalates between GC DNA base pairs. Favour adjacent G base pairs on adjacent strands. Intercalation helped by aromatic pi-pi interaction of tricyclic ring and DNA bases. Interaction further stabilized by hydrogen bonding between nucleic acid and moelcule. Interupts topoisomerase II activity leading to disruption in replication and transcription processes.
• Cytotoxic agents – naturally occuring: vinca alkaloids (VA): semi synthetic compound called vinfluenine has similar properties to the VA. Members of VA are vincristine, vinblastine and vindesine.
• VA mechanism of action – tubulin important for microtubule formation through polymerization. Drug binding prevents tubulin polymerization. Spindle formation is prevented during cell division. These are known as spindle poison. Cell cycle stops at metaphase of mitosis.
• Alkylating agents – mechanism of action

  Through electrophilic groups, alkylating agents form covalent bonds with DNA. Happens during DNA replication. Unpaired nucleotides are more prone to alkylation. This leads to covalent bond formation by the agents.
• DNA base targeting – alkylating agents have highly electrophilic groups that are attracted to nucleophilic groups (N7) on guanine. This forms covalent bond, disrupting DNA functions.
• Alkylating anti-cancer agents – two nucleophilic groups present leads to inter/intrastrand crosslinking forming. Leads to miscoding due to alkylation of nucleic acids.