Wonder Drugs

Suly V. Gonzalez and Eric J. Marsh

Background
Ancient cultures and societies used wonder drugs
Quinine
from Cinchona trees in South America
Treats fevers and is an antimalarial

Foxglove
Contains digitalis (substance that stimulates heart muscles)
Used for heart ailments in Western Europe
Is still prescribed as heart stimulant

Seed capsules of a poppy plant

Historically not many things were successfully used for

bacterial infections.

Small cuts and wounds would be life

threatening if infected

Aspirin and Dyes

Bayer and Company
Originally a dye company
Interested in chemical production of medication - especially aspirin

Felix Hofmann - Chemist

Investigated properties of compounds of salicylic acid
Bark of trees of the willow genus

Aspirin - Salicin
Breaks up into two parts
Glucose
Salicyl alcohol
If oxidized produces salicylic acid
Salicylic Acid reduces fever, relieves pains, and acts as anti-inflammatory
Harmful to stomach lining
Reduced medicinal value

Aspirin - Acetyl Salicylic Acid

Hoffman took H of the phenol group and replaced it with acetyl group (CH 3CO)
Hoped this would remove harmful effect but keep anti-inflammatory property
Phenol group is what makes it corrosive

Note: this was already done by another German chemist 40 years before

Aspirin - In the End

Hofmanns experiments paid off - for both his pops (had rheumatoid arthritis) and
the Bayer company
1899 Bayer company began marketing powder aspirin
Aspirin name
A from Acetyl
Spir from Spiraea ulmaria, the meadowsweet plant

The Saga of Sulfa - The History

Dr. Paul Ehrilch - no training in experimental chemistry or applied technology
Noted coal tar dyes would stain some tissue and some microorganisms but not
others.
Came up reasoning of how to kill tissue with this

Magic bullet approach

Magic bullet = dye that targeting the tissue it stained

First Success
Trypan red I dye
Used against trypanosomes - protozoic parasite- in lab mice
Although worked in the mice it did not work for the human disease (african
sleeping sickness).

Syphilis
Ehrlich looked for magic bullet for syphilis
At the time syphilis treated with mercury - not very good for the patients

Found Number 606 - arsenic containing aromatic compound

Compared to mercury treatment it was good
Had some toxic side effects
Didnt always cure patients with syphilis

Ehrlich came up with chemotherapy

Experimenting on Daughters
Dr. Gerhard Dogmak decided to use a dye called prontosil redi to treat his
daughter
Had already been experimenting with it but hadnt found any activity against
bacteria
Gave to his daughter orally, her recovery was fast
Recovery wasnt because of dye but how it broke down in human body

Structure of Different Sulfa Drugs

Sulfanilamide is a result of the breaking down of prontosil red in the human
body
Prontosil red

Minor Changes in Sulfa Drug

structures are capable of
changing what the are able to
deal with

Sulfanilamide

SulfapyridinePneumonia

SulfacetamideUrinary tract
infection

SulfathiazoleGastrointestinal
infections

How the Sulfas kill bacteria

Bacteria need Folic Acid
Similarity between Sulfa
Drugs and Folic Acid paminobenzoic acid molecules

Bacteria confuse the Sulfa molecule and Folic acid p-aminobenzoic acid and die from
Malnutrition

Penicillins-the earliest true antibiotics

Notable Scientists
Louis Pasteur 1877First to show one microorganism could be used to kill another when he found
common bacteria could prevent a strain of anthrax in urine
Joseph Lister
Cured abscesses in patients with Penicillium mold extract

Alexander Fleming
1928-Found Penicillium mold killed staphylococci bacteria colony

Penicillium notatum found by him to be effective 800 times diluted

Early Trials
Injected in mice without toxic effects-applied directly to infected tissues
Animal Cell Membranes Vs. Cell Walls
Human trials
Short lived success in adults
More reliable success in children

Structure
The structure of penicillin was discovered in 1946 and synthesized for the
first time in 1957
Beta-Lactam Ring
Ring Strain and Instability

How Penicillin works

Beta-Lactam Rings open in the presence of the enzyme that creates bacterial walls
An OH group on the bacterial enzyme is acylated
-Acyl Group
-Deactivation

Different strains of Penicillins are mostly identical except for areas that may vary
from strain to strain

Strains of
Penicillins

Pen. G

Amox.

Ampi.

Peni O.

Clox.