Chemotherapy Using Compounds of Inorganic Elements

1. Chemotherapy Using Compounds of Inorganic Elements DR. Sherin Bakhashab

2. Metal ions in medicine • Metals in medicine are used in organic systems for diagnosis and treatment purposes. • Metal ions are often used for diagnostic medical imaging. • Metal complexes can be used either for radioisotope imaging (from their emitted radiation), for example in magnetic resonance imaging (MRI)

3. Examples of metals used for diagnosis • Technetium: Tc is the most commonly used radioisotope agent for imaging purposes. It has a short half-life, emits only γ-ray photons, and thus is particularly suitable as an imaging radioisotope. • Cobalt (III): Co is used with the compound bleomycin, which is an antibiotic, to be selectively taken by tumour cells. The use of Co which has the best distribution ratio, but its half-life is too long to be used for imaging purposes. Cobalt

4. Metals in treatment • Metals have been used in treatments since ancient times. • Sodium vanadate has been used since the early 20th century to treat rheumatoid arthritis. • Recently metals have been used to treat cancer, by specifically attacking cancer cells and interacting directly with DNA. The positive charge on most metals can interact with the negative charge of the phosphate backbone of DNA. • Some drugs developed that include metals interact directly with other metals already present in protein active sites. • Other drugs can use metals to interact with amino acids with highest reduction potential.

5. Examples of metals used in treatment • Platinum: platinum based compounds have been shown to specifically effect head and neck tumors. • Gold: gold salt complexes have been used to treat rheumatoid arthritis. • Zinc: it is used topically to heal wounds. • Silver: has been used to prevent infection at the burn site. • Platinum, Titanium, Vanadium, Iron: have been shown to react with DNA specifically in tumor cells to treat patients with cancer. • Gold, silver , copper: phosphine ligand compounds containing gold, silver and copper have anti-cancer properties.

6. Cisplatin • Cisplatin is a chemotherapy drug, it was the first member of a class of platinum-containing anti-cancer drugs. • Cisplatin is administered intravenously as short-term infusion in normal saline for treatment of solid malignancies. • It is used to treat various types of cancers, including sarcomas (a malignant tumour of connective or other non-epithelial tissue) and some carcinomas (a type of cancer that develops from epithelial cells, e.g. lung cancer, ovarian cancer, and lymphomas).

7. Mechanism of action

8. Mechanism of action • Cisplatin binds to DNA, and causes a critical structural change by bending DNA 45 degrees ( form cross-linking) and therefore inhibit DNA synthesis.

9. Side effects • Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient’s creatinine (a measure of renal function) is high. • Myelotoxicity: This agent can cause bone marrow suppression • Hemolytic anemia • Neurotoxicity (nerve damage) • Nausea and vomiting • Ototoxicity (hearing loss)

10. References • http://www.chem.gla.ac.uk/cornin/teaching.php • Dabrowiak. James C. ‘Metals in Medicine’. Inorganic Chemica Acta. (2012)