Drug Action -

Claudelle Calfat

Objectives:
D.8.1 Describe the importance of geometrical isomerism in drug action
D.8.2 Discuss the importance of chirality in drug action


Drugs can be classified different ways:
--Therapeutic effect: Drugs can be classified by the effect they have on an organism. The negative aspect of this is that one grouping of drug will have a very varied assortment of drugs, simply all with a similar effect. The drugs themselves can be quite different.
--Structure: Drugs can be classified according to their general structure in order to see how it effects their mode of action, or essentially how a drug effects a living organism. Different chemical structures to sort by may include stereoisomerism, the ring strain of a beta-lactum ring, or sorted by solubility and uptake.


Stereoisomerism


Isomer vs. Stereoisomer

Isomers are different compounds that have the same molecular formula.

Stereoisomerism is the different spatial arrangements of atoms in molecules. There are 2 main types, Geometric Isomerism and Optical Isomerism.

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Geometric Isomerism
  • restricted rotation around atoms due to carbon-carbon double bonds.
  • Can exist in both organic and inorganic compounds
  • Two types:
    • Cis- isomer- (cisplatin) when 2 gorups are on the same side of the double bond and bonded to 2 different carbon atoms
    • Trans- isomer- (transplatin) when 2 functional groups are bonded to opposite sides of the double bond

Compare:
Cis
Trans
Same side of double bond
Opposite side of double bond
Effective anti-cancer drug
Ineffective anti-cancer drug
No overall charge





cis.gif

Cisplatin
Due to cisplatins lack of overall charge, it can diffuse thourgh the cancer cell’s membrane. Once there, it exchanges a chloride ion for a molecule of water to form [Pt(NH3)2Cl(H2O)]+This ion enters the cell nucleus, binding to the DNA by exchanging another chloride ion to form
[Pt(NH3)2(DNA)]2+.This alters the DNA so that when it tries to replicate, the DNA cannot be copied correctly and the cell dies.


Chirality in Drug Action
A chiral molecule is a type of molecule that lacks an internal plane of symmetry, and so has a mirror image.
chirality.jpg
Chiral carbon atoms, or asymmetrical carbon atoms, form two different optically active forms, behaving in different ways in the body due to their different stereochemistry. One enantiomer, or mirror image, of the thalidomide gives the benefits associated with the drug, while the other is responsible for the side effects and fetal deformities. When drugs are synthesized, both forms are studied separately.







sources:
http://www.thefreedictionary.com/mechanism+of+action
http://www.studyvilla.com/isomerism.aspx
http://www.emeraldinsight.com/fig/0170950206002.png
http://chirbase.u-3mrs.fr/chirality/laboratory/en/pres.htm