Thursday, April 7, 2011

IB Chemistry in Medicine and Drugs

Stereoisomers, Enantiomers and Optical Isomers
Stereoisomerism are isomers with same Molecular Formula + Structural Formula but different in spatial arrangement ( different 3 Dimensional shapes )

2 types of stereoisomers  for ORGANIC compounds
  • geometrical
  • optical 

Optical Isomers (ORGANIC)
  • Chiral or Asymmetrical Carbon 
  • 4 different gps attached to carbon central
  • Non superimposable
  • Mirror image ( right, left handed )
  • Enantiomers
  • Identical chemical/physical properties 
  • 2 enantiomers rotate plane of polarised light to diff directions
Optical isomers (Thalidomide) tragedy due to Mirror Image
Thalidomide drug exist as optical isomers, 
  • Enantiomers (R) and (S)
  • (R) effective against  insomnia and morning sickness
  • (S) teratogenic, birth and limb defect



In nature, our body synthesises enzyme which have active site for only one enantiomer
  • Drug company, synthesise racemic mix (R)/(S) which is cheaper.
  • (R) is effective but (S) has side effect.
  • Enzyme recognises only one enantiomer due to active site



Mirror image of thalidomide caused limb deformation
  • (S) enantiomer causes limb defects and severe shortening of the arms /legs.
  • (R) enantiomer is effective drug
  • Body will convert (R) to (S) by racemisation process, producing a racemic mixture (R)/(S)

Mirror Image of Ibuprofen (pain killer drug) has no side effect
  • (S) enantiomer, effective in reducing fever and pain relief
  • (R) enantiomer has no side effect
  • Most drugs in racemic mix equal (R) and (S)
  • Cheaper to synthesise racemic mix
  • Single enantiomer (Expensive) but appears to be more effective than racemic mix
  • Clinical trial essential to ensure no harmful side effect
  • Most racemic drugs (R)/(S) have little side effect
  • Thalidomide (R)/(S) was disaster!!!!!!



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    IB Keywords
    • Enantiomers - pair of non superimposable isomer, (mirror image), (diff 3D shapes)
    • Isomers - compounds with same MF + SF but diff spatial arrangement
    • Racemic - equal (50/50)% mixture of both enantiomers (S) and (R) ( optically inactive ), no net rotation of plane-polarized light, rotations cancel out each other, present in equal amounts.
    History of Thalidomide
    1954 -   Thalidomide for  insomnia and morning sickness.
    1961 -   Withdrawn, teratogenicity, birth defects, if drug is taken during pregnancy.

    1990 - FDA approved  for erythema nodosum leprosum,  leprosy (skin disease) 
    1998 -  FDA approved for multiple myeloma, (cancer of plasma cells in the blood) 

    2004 - Lenalidomide derived from Thalido able to strengthen immune cells and effective against blood cancers
    2011 - Thalidomide + Lenalidomide inhibit formation of new blood vessels ( anti-angiogenic) of tumor cells, Tumors unable to grow/spread due to lack of nutrition. Researchers testing thalidomide in trials for  HIV and Crohn’s disease.
    Video Tutorial, Stereoisomerism, Enantiomers, Optical Isomers
    ......................................................................................................................................................
    Video, Thalidomide, Enantiomers/Mirror Image/Chiral Carbon
    Thalidomide making a come back after named as the greatest disaster in medical history

    Click HERE to view video on the Return of Thalidomide/Lenalidomide
    Keynotes from video 
    • Why rejuvenate it despite so deadly to pregnant women?
    • Able to treat Blood and Bone marrow Cancer.
    • Kept away for 20 yrs since disaster, rejuvenated after 30% cancer patient recovered
    • Caution and seek professional medical advice
    • No pregnant women allowed, US approved it
    • Why no new drugs to replace old Thalidomide drug?
    .....................................................................................................................................................
    Scientists discovered How Thalidomide caused Malformed Limbs
    March 2010 - Published in Science by Takumi Ito.
    Click HERE for info/source
    Defect Limbs due to Thalidomide
    • (S) enantiomers binds/inactivates the protein cereblon, which is important in limb formation. Inactivation, leads to a teratogenic effect on LIMB DEFORMITIES

    Published in Science, March 2010
    • Hiroshi Handa /Takumi Ito - Developed tiny beads (200 nm) with Thalidomide attached.
    • Thalidomide beads mix with cells extract
    • Protein Cereblon was bounded on beads
    • Lack of Protein Cereblon during embryo development, causes limb deformities



    Thanks to all pictures and video contributors for the above post

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