AP Chemistry Final Project - Thalidomide

Thalidomide

How are the side

effects caused?

• breaks into compounds in the body that last 40x longer than drug
• production of ROS disrupts normal embryonic development
• DNA damage caused by ROS and free radicals

Chirality

• Abundant
• mirror image is different
• Thalidomide
• Optical isomers have the same sequence of atoms and bonds but are different in their 3D shape

Sites:

http://www.news-medical.net/health/Thalidomide-Uses.aspx

http://www.news-medical.net/health/What-is-Peripheral-Neuropathy.aspx

http://www.news-medical.net/health/Thalidomide-Side-Effects.aspx

http://www.news-medical.net/drugs/Thalomid.aspx

http://www.sciencedaily.com/releases/2011/04/110419111503.htm

http://myeloma.org/pdfs/Understanding_Thalidomide.pdf

http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/thalidomide

http://www.drugs.com/food-interactions/thalidomide.html

http://www.medicinenet.com/thalidomide/article.htm

http://www.webmd.com/drugs/drug-16403-Thalomid+Oral.aspx?drugid=16403&drugname=Thalomid+Oral

Images:

http://chemwiki.ucdavis.edu/@api/deki/files/4830/image074.png?size=bestfit&width=219&height=152&revision=1

http://www.studydroid.com/imageCards/0n/aj/card-24464782-back.jpg

http://upload.wikimedia.org/wikipedia/commons/a/a5/NCP14053.jpg

http://images.smh.com.au/2012/07/25/3488000/art-thalidomide-620x349.jpg

http://helix.northwestern.edu/sites/helix/files/styles/16by9/public/legacy_files/image-1_2.jpeg?itok=mGmk0CGT

http://images.radiopaedia.org/images/4669644/f69d5093f78242a52cbfe0fa60488f_gallery.jpg

http://www.learningradiology.com/caseofweek/caseoftheweekpix2009-365/cow365-arr.jpg

http://images.radiopaedia.org/images/4669603/6af69fa832841643bddf9063d31a5d_gallery.jpg

Side Effects- Continued

~Morning Sickness Drug not meant for Pregnant Women~

Bibliography

• mostly famous for its tragic side effects of inducing birth defects and peripheral neuropathy (damage to PNS)
• has been called "one of the biggest medical tragedies of modern times"

Optical Isomerism

**Note: This is not the complete list of possible side effects. Consumers of the drug should consult a

doctor/health professional if they experience

any discomfort/other side effects.

• Left hand Right Hand molecules
• R stands for Latin "rectus" for right
• S stands for Latin "sinister" for left

Functional Groups Present in the Molecule

Side Effects

• fatigue
• constipation
• increased risk of deep vein thrombosis (blood clot)
• high doses can cause pulmonary oedema, atelectasis, aspiration pneumonia and refractory hypotension
• increased side effects in multiple myeloma patients who use thalidomide combined with other drugs for treatment

• 2 ketone groups
• 2 amide groups
• a cyclohexene
• a cyclohexane
• a cyclopentane (Solomons)

Uses

Molecular Formula: C13H10N2O4

Average mass: 258.23 g/mol-

Why this topic?

• Thalomid capsules = standard treatment for multiple myeloma (cancer affecting the bone marrow)
• anti-inflammatory effects in actinic prurigo (autoimmune skin disease)
• causes angiogenesis, which can be included as a side effect but also helps in treating macular degeneartion and lesions caused by Kaposi's sarcoma in AIDS patients
• treatment and prevention of skin symptoms associated with ENLin leprosy patients

By: Reisa Matsuda, and Rika Sato

• interest in medical topics
• real life application
• physiological mechanisms

Molecular Structure

Systematic name:

(RS)-2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione

• acidic hydrogen at the chiral center
• Left hand, Right hand molecules.

History

Aftermath

• Publication of Thalidomide increased significantly
• BUT...1988, approved by FDA as a treatment for leprosy, multiple myeloma (cancer)
• Currently ongoing studies to treat other diseases as well

-Overview-

How It Works

• 1954: developed by German pharmaceutical company
• a wonder drug (tranquiliser) for treating insomnia, coughs, colds and headaches.
• ALSO, morning sickness drug for pregnant women
• 1960: A generation of kids with birth defects. Scientists suspects...
• 1962: US enacted laws requiring tests for safety during pregnancy before a drug can receive approval for sale in the U.S.

Mechanism of

Thalidomide Synthesis

• exact mechanism is unclear
• immuno-modulating agent => works by acting on the cells involved in the body's immune system, affects functions
• angiogenesis
• 2 effects on cancer:

1. boost body’s immune response

2. block the blood supply of cancerous tumors

1. Intercalates to the DNA

=>flat structure = slide into gaps between the subunits of the DNA molecule

2. Intercalation is not at random

=> Thalidomide is composed of three attached rings, two of which look in overall structure almost identical to guanine and adenine

3. interferes with the production of certain proteins

4. interfere with angiogenesis

=> reduction in overall limb size

** four puzzle pieces have been identified, but unclear how they worked together.

Future of Medicine

What is Thalidomide?

• Excessive reliance on Animal testing
• Limited technological resources and scientific knowledge during the 1950s

• Changed the standards of pharmaceutical industry
• FDA Regulation
• Chemistry changed medicine!

Example of an intercalating drug (red and grey) into DNA helix (green)