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• Cisplatin

  A) Cisplatin

  B) Pt

  C) NH3

  D) NH3

  E) Cl

  F) Cl

  
• Trans isomer

  A) Trans platin

  B) Cl

  C) NH3

  D) NH3

  E) Cl

  
• Treatment of cancer – use of cisplatin to stop cancer cell division without maximum damage to host cell. Reduces tumour size at much lower dose.
• Side effects of cisplatin – anti cancer drugs usually affects both healthy and cancer cells leading to hair loss and nausea.

  Cisplatin kidney damage, nausea, vomiting, hair loss, bone marrow suppression and ear damage.
• Cisplatin is used in combination chemotherapy with drugs like vinblastine.
• Mechanism of action – cisplatin forms intrastrand crosslinks with DNA. The Cl molecules of cisplatin is replaced by water molecules through hydrolysis. These are then replaced by nitrogen bases in DNA. Leads to disruption in DNA structure. Not recognized by repair mechanisms. This affects replication and transcription. Leads to apoptosis.
• The different chloride ion concentration leads to cisplatin behaving different inside and outside cell. Outside cells, hydrolysis not occurs as there is high chloride conc. Allows neutral cisplatin to pass through.

  Hydrolysis happens inside the cell with low chloride concentrations. Forms positively charged complex. This is attracted to negatively charged DNA backbone. Binding to DNA can form intrastrand adducts. This can also affect RNA and mitochondrial DNA which inactivates them.
• Platinated DNA – DNA replication is blocked since cisplatin can cause bends in the DNA structure.
• HMG proteins and cisplatin cytotoxicity – DNA modified by cisplatin gets attracted to HMG proteins. The modified DNA strand acts like a binding site to the HMG proteins which interfere with the cellular mechanism's of DNA like replication and transcription.
• Trans-platin inactive – hydrolysis of trans platin leads to replacement of Cl- ligands with water. It is hard to replace the NH3 ligands. Intrastrand adduct is formed similar to cisplatin when the other water ligand is not in the right position to be replaced by the N on guanine. NH3 presence interferes with this process.