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Metal Ions In Medicine



         SAKHARKAR MOHD ANZAR
                               MSC-I
                              SEM-II
            INORGANIC CHEMISTRY
      Ramniranjan Jhunhunwala college

              2/12/2013   By Mohd Anzar Sakharkar   1
Metal Ions in Medicine
 Metals in medicine are used in organic
  systems for diagnostic and treatment
  purposes.
 Inorganic elements are also essential for
  organic life as cofactors in enzymes
  called Metalloproteins.
 When metals are scarce or high
  quantities, equilibrium is set out of balance
  and must be returned to its natural state.

                      2/12/2013   By Mohd Anzar Sakharkar   2
Metals in diagnosis
   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).




                        2/12/2013   By Mohd Anzar Structure
                                                  Sakharkar   3
Examples of metals used for
diagnosis:Tc is the most commonly used
 Technetium:
  radioisotope agent for imaging purposes. It has a
  short half-life, emits only γ ray photons, and does
  not emit β or α particles and thus is particularly
  suitable as an imaging radioisotope.
 Gadolinium(III), Iron(III), Manganese(II): For MRI
  imaging paramagnetic metals are needed for
  contrast imaging. Gd(III), Fe(III), and Mn(II) are all
  paramagnetic metals that are able to alter the
  tissue relaxation times and produce a contrast
  image.
 Cobalt(III): Co(III) is used with the compound
  bleomycin, which is an antibiotic, to be selectively
  be taken up by tumor cells. The use of Co results
  in the best blood-to-tumor distribution ratio, but its
  half-life is too long to be conducive for imaging
  purposes                   2/12/2013 By Mohd Anzar Sakharkar 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, while other drugs can use metals to
  interact with amino acids with the highest reduction
  potential.


                       Cisplatin, a platinum Anzar Sakharkar complex.
                             2/12/2013 By Mohd
                                               coordination             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: Zinc can be used topically to heal wounds. Zn2+ can be
    used to treat the herpes virus.
   Silver: Silver has been used to prevent infection at the burn
    site for burn wound patients.
   Tungsten: Tungsten polyoxoanions can be used to treat AIDS.
   Platinum, Titanium, Vandium, Iron: cis DDP (cis-
    diaminedichoroplatinum), titanium, vanadium, and 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.


                                2/12/2013   By Mohd Anzar Sakharkar   6
Cisplatin
   Cisplatin, cisplatinum, or cis-
    diamminedichloroplatinum(II)
    (CDDP) is a chemotherapy drug. It
    was the first member of a class of
    platinum-containing anti-cancer drugs.




                    2/12/2013   By Mohd Anzar Sakharkar   7
 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, some carcinomas (e.g.
  small cell lung cancer, and ovarian cancer),
  lymphomas, and germ cell tumors.
 Cisplatin is particularly effective against
  testicular cancer; the cure rate was improved
  from 10% to 85%



                       2/12/2013   By Mohd Anzar Sakharkar   8
Mechanism of action
 Following administration, one of the chloride ligands is
  slowly displaced by water in a process termed
  aquation.
 The aqua ligand in the resulting [PtCl(H2O)(NH3)2]+ is
  itself easily displaced, allowing the platinum atom to
  bind to bases.
 Of the bases on DNA, guanine is preferred.
 Subsequent to formation of [PtCl(guanine-
  DNA)(NH3)2]+, cross-linking can occur via displacement
  of the other chloride ligand, typically by another
  guanine.
 The damaged DNA elicits DNA repair mechanisms,
  which in turn activate apoptosis when repair proves
  impossible.
                            2/12/2013   By Mohd Anzar Sakharkar   9
DNA binding
    Cisplatin binds to DNA and causes a
    critical structural change in the DNA –
    a bend of 45 degrees.




                     2/12/2013   By Mohd Anzar Sakharkar   10
Cisplatin resistance
 Cisplatin combination chemotherapy is the
  cornerstone of treatment of many cancers.
 Initial platinum responsiveness is high but the
  majority of cancer patients will eventually
  relapse with cisplatin-resistant disease.
 Oxaliplatin is active in highly cisplatin-resistant
  cancer cells in the laboratory; however, there
  is little evidence for its activity in the clinical
  treatment of patients with cisplatin-resistant
  cancer
 The drug paclitaxel may be useful in the
  treatment of cisplatin-resistant cancer; the
  mechanism for this activity is unknown.
                          2/12/2013   By Mohd Anzar Sakharkar   11
Carboplatin
   Carboplatin, or cis-Diammine(1,1-
    cyclobutanedicarboxylato)platinum
    (II) is a chemotherapy drug used
    against some forms of cancer (mainly
    ovarian carcinoma, lung, head and
    neck cancers)




                    2/12/2013   By Mohd Anzar Sakharkar   12
Related compound




          2/12/2013   By Mohd Anzar Sakharkar   13
Side effects
 Nephrotoxicity (kidney damage) is a major
  concern. The dose is reduced when the
  patient's creatinine clearance (a measure
  of renal function) is reduced.
 Myelotoxicity: This agent can also cause
  profound bone marrow suppression.[15]
 Hemolytic anemia can be developed after
  several courses of cisplatin. It is
  suggested that an antibody reacting with a
  cisplatin-red-cell membrane is responsible
  for hemolysis.[16] 2/12/2013   By Mohd Anzar Sakharkar   14
 Neurotoxicity (nerve damage) can be
  anticipated by performing nerve conduction
  studies before and after treatment.
 Nausea and vomiting: cisplatin is one of the
  most emetogenic chemotherapy agents.
 Ototoxicity (hearing loss): there is at present
  no effective treatment to prevent this side
  effect, which may be severe.
 Electrolyte disturbance: Cisplatin can cause
  hypomagnesaemia, hypokalaemia and
  hypocalcaemia. The hypocalcaemia seems
  to occur in those with low serum magnesium
  secondary to cisplatin, so it is not primarily
  due to the Cisplatin.
                        2/12/2013   By Mohd Anzar Sakharkar   15
BIBILIOGRAPHY
 http://www.chem.gla.ac.uk/cronin/teac
  hing.php
 Dabrowiak, James C. “Metals in
  Medicine.” Inorganic Chemica Acta.
  (2012)




                  2/12/2013   By Mohd Anzar Sakharkar   16

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Metal Ions in Medicine and Diagnosis

  • 1. Metal Ions In Medicine SAKHARKAR MOHD ANZAR MSC-I SEM-II INORGANIC CHEMISTRY Ramniranjan Jhunhunwala college 2/12/2013 By Mohd Anzar Sakharkar 1
  • 2. Metal Ions in Medicine  Metals in medicine are used in organic systems for diagnostic and treatment purposes.  Inorganic elements are also essential for organic life as cofactors in enzymes called Metalloproteins.  When metals are scarce or high quantities, equilibrium is set out of balance and must be returned to its natural state. 2/12/2013 By Mohd Anzar Sakharkar 2
  • 3. Metals in diagnosis  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). 2/12/2013 By Mohd Anzar Structure Sakharkar 3
  • 4. Examples of metals used for diagnosis:Tc is the most commonly used  Technetium: radioisotope agent for imaging purposes. It has a short half-life, emits only γ ray photons, and does not emit β or α particles and thus is particularly suitable as an imaging radioisotope.  Gadolinium(III), Iron(III), Manganese(II): For MRI imaging paramagnetic metals are needed for contrast imaging. Gd(III), Fe(III), and Mn(II) are all paramagnetic metals that are able to alter the tissue relaxation times and produce a contrast image.  Cobalt(III): Co(III) is used with the compound bleomycin, which is an antibiotic, to be selectively be taken up by tumor cells. The use of Co results in the best blood-to-tumor distribution ratio, but its half-life is too long to be conducive for imaging purposes 2/12/2013 By Mohd Anzar Sakharkar 4
  • 5. 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, while other drugs can use metals to interact with amino acids with the highest reduction potential. Cisplatin, a platinum Anzar Sakharkar complex. 2/12/2013 By Mohd coordination 5
  • 6. 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: Zinc can be used topically to heal wounds. Zn2+ can be used to treat the herpes virus.  Silver: Silver has been used to prevent infection at the burn site for burn wound patients.  Tungsten: Tungsten polyoxoanions can be used to treat AIDS.  Platinum, Titanium, Vandium, Iron: cis DDP (cis- diaminedichoroplatinum), titanium, vanadium, and 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. 2/12/2013 By Mohd Anzar Sakharkar 6
  • 7. Cisplatin  Cisplatin, cisplatinum, or cis- diamminedichloroplatinum(II) (CDDP) is a chemotherapy drug. It was the first member of a class of platinum-containing anti-cancer drugs. 2/12/2013 By Mohd Anzar Sakharkar 7
  • 8.  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, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors.  Cisplatin is particularly effective against testicular cancer; the cure rate was improved from 10% to 85% 2/12/2013 By Mohd Anzar Sakharkar 8
  • 9. Mechanism of action  Following administration, one of the chloride ligands is slowly displaced by water in a process termed aquation.  The aqua ligand in the resulting [PtCl(H2O)(NH3)2]+ is itself easily displaced, allowing the platinum atom to bind to bases.  Of the bases on DNA, guanine is preferred.  Subsequent to formation of [PtCl(guanine- DNA)(NH3)2]+, cross-linking can occur via displacement of the other chloride ligand, typically by another guanine.  The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible. 2/12/2013 By Mohd Anzar Sakharkar 9
  • 10. DNA binding  Cisplatin binds to DNA and causes a critical structural change in the DNA – a bend of 45 degrees. 2/12/2013 By Mohd Anzar Sakharkar 10
  • 11. Cisplatin resistance  Cisplatin combination chemotherapy is the cornerstone of treatment of many cancers.  Initial platinum responsiveness is high but the majority of cancer patients will eventually relapse with cisplatin-resistant disease.  Oxaliplatin is active in highly cisplatin-resistant cancer cells in the laboratory; however, there is little evidence for its activity in the clinical treatment of patients with cisplatin-resistant cancer  The drug paclitaxel may be useful in the treatment of cisplatin-resistant cancer; the mechanism for this activity is unknown. 2/12/2013 By Mohd Anzar Sakharkar 11
  • 12. Carboplatin  Carboplatin, or cis-Diammine(1,1- cyclobutanedicarboxylato)platinum (II) is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers) 2/12/2013 By Mohd Anzar Sakharkar 12
  • 13. Related compound 2/12/2013 By Mohd Anzar Sakharkar 13
  • 14. Side effects  Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient's creatinine clearance (a measure of renal function) is reduced.  Myelotoxicity: This agent can also cause profound bone marrow suppression.[15]  Hemolytic anemia can be developed after several courses of cisplatin. It is suggested that an antibody reacting with a cisplatin-red-cell membrane is responsible for hemolysis.[16] 2/12/2013 By Mohd Anzar Sakharkar 14
  • 15.  Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment.  Nausea and vomiting: cisplatin is one of the most emetogenic chemotherapy agents.  Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe.  Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the Cisplatin. 2/12/2013 By Mohd Anzar Sakharkar 15
  • 16. BIBILIOGRAPHY  http://www.chem.gla.ac.uk/cronin/teac hing.php  Dabrowiak, James C. “Metals in Medicine.” Inorganic Chemica Acta. (2012) 2/12/2013 By Mohd Anzar Sakharkar 16