different metals for treating diseases @acs @science @chemistry

1. Muqaddas Baigum 19121707-005
M.Phil chemistry 1st Spring 2019
Uses of inorganic compounds in the treatment of diseases
MEDICINAL USES OF TRANSITION BASED
COMPOUNDS
CHEM-513
DR.SAJJAD HUSSAIN SUMRRA
1

2. TABLE OF CONTENTS
1.
CONTENTS SLIDE NUMBER
INTRODUCTION 3
GENERAL EXAMPLES 4
CIS PLATIN AND RELATED COMPLEXES 6
STRUCTURE OF CIS PLATIN 7
HOW CANCER OCCURE 8
MECHANISM OF ACTION 9
EFFECTIVENESS OF CIS PLATIN 10
REQUIRMENTS 11
INTAKE OF PLATINUM DRUG 12
AURANIFINS AND ARTHRITIS TREATMENT 13
MECHANISM 14
TOXICITY 15
VANADIUM COMPLEXES 16
MECHANISM OF ACTION 17
2

3. Historically, number of compounds have been used in
medicines, including arsenic compounds for the
treatment of syphilis*
General examples of compounds.
1. Lithium Brain(hyperactivity)
2. Gold Arthritis
3. Barium sulfate Imaging Agent
INTRODUCTION
3G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg628.

4. There are other examples in ordinary use.
1. Antacids .
2. Fluoride as tooth decay preventative.
3. And other drugs using copper, zinc and tin.
4. We will describe only three groups of these
compounds.
Continue…..
4G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg628.

5. 1. The anticancer platinum complexes
2. Gold compounds used in arthritis treatment
3. Vanadium compounds used in diabetes and cancer
treatment
Countinue…….
5G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg628.

6. Discovery
• Its discovery as anticancer agent was discovered by B.
Rosenberg
How?
• When E. coli bacteria laced in an electric field stopped
dividing and grew into long filaments similar to their
action when treated with antitumor agents.
 Cisplatin and related compounds
6chem. Eng. News, june 21 1999, p. 9.

7. Structure of cisplatin
7G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg628.

8. • It’s a genetic diorder.
• DNA is the form of life. It replicates to intsruct the form
of life i.e cell.
• Uncontrolled replication of DNA causes the
uncontrolled cell production an hence causing the
cancer.
How cancer occurs?
8G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg629.

9. • Hydrolysis of cisplatin to diaquo complex.
• Cross linkage between adjacent Guanine base.
• Kink in DNA helix within the same strand with an angle
upto 34 degree.
• This changes the shape and controls the self replication
hence cancer.
Mechanism of treatment
9G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg630.

10. • Trans isomer is inactive as an anticancer agent.
o Reason
• Cannot form a cross linkage between guanine bases.
Due to steric reasons.
• It is very labile, undergo rapid nucleophilic substitution
before reaching prime target.
Preferred isomers
10
G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg628.U.-M. Ohndorf, M. A. Rould, Q. He, C O. and S. j.
Lippard, Nature, 1999, 399, 708.

11. 1. A pair of hard (chloride or oxygen donors) cis-ionic
ligands subject to substitution by DNA nitrogen base.
2. Water solubility and ability to pass through cell
membrane (uncharged complexes).
3. Unreactive ligands on the other site that are primary or
secondary amines.
Requirements for an effective mutagenic agents.
11
D. B. Brown, A. R. Khokhar, M. P. Hacker, j. j. MacCormack, and R. A.
Newman, synthesis and biological studies of a new class of Anti
tumor platinum complexes'' in S. j. Lippard ed., Pt, Au, and other
metal chemotheraputic chemical society,

12. 1. Cisplatin is administered interavenously.
2. One Pt(lV) bis-(acetato-
O)amminedichlorobis(cyclohexaneamine)platinum(IV)
is tested as orally active antitumor agent.
Intake of platinum drugs
12
FIGURE 1 bis-(acetato-
O)amminedichlorobis(cyclohexan
eamine)platinum(IV)
C. M. Giandomenico, M. J. Abrams, B. A. Murrer, j. F. Vollano, M. I.
et all inor. che,., 1995, 34, 1015.

13. Gold in many forms has been used medicinally for
hundred of years .
• More recently, the compound auranofins, has been
developed.
13
 AURANOFIN AND ARTHRITIS
TREATMENT
FIGURE 2 Auranofin
G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg632.

14. • The major disadvantage of thiol complexes of gold are
that the must be administered by injection into the site of
inflammation.
14
Toxicity 0f Auranofins
G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg632.

15.  The one possibility of action is through the formation of;
1. Gold- sulpher complexes
2. Which inhibit the di sulfide bond formation
15
Mechanism of action
G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg632.

16. Several vanadium complexes have been found to have
insulin like activity.
• Intake;
1. (Dipicolinate )Oxo vanadate(V)
2. [VO2dipic]̄ .
Are considered to be effective as an oral agents in animals
16
 Vanadium complexes in medicine
G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg632.
Structure 2

17. The acid base properties of the compound make it likely
to be absorbed in the acidic environment of stomach or
the first part of the small intestine ; it protonates at pH
aproximately 1.
17
Mechanism of action
G. L. Miessler, Donald A. Tarr,inorganic chemistry 3rd
eddition,pg632.