PHAL211
Drug discovery
1st antibiotics
The first antimicrobial called aniline came about in the 1850s
This was an reaction between nitrobenzene, iron and hydrochloric acid
Then in 1859 atoxyl came around by reacting aniline with arsenic
1st attempts at discovery
Friedrich Bayer company explored antibacterial activity of azo dye derivatives in the 1920s
Prontosil was then identified and commercialized in 1935
From this base drug prontosil they made over 5000 derivatives of this base compound, and we call these
sulfadrugs
1st screening platform
What people find interesting about this accidental discovery is that microbes were competing against each
other and producing compounds that we might find useful
Before this accidental discovery medicine was solely a chemistry perspective. So this accidental discovery This
opened up the idea that there will be a range of compounds out in nature and perhaps produces by different
microbes that we could utilize to target the microbes ourselves.
So, this set up the first screening platform called the Waksman platform
What Waksman discovered was that soil bacteria can inhibit growth of other bacteria
So, he made this platform to screen huge number of organisms for their compounds at once and see what
those compounds were
Antibiotic expansion by semi-synthesis
When we found each of these classes through these screening protocols, we could then take those antibiotics
and bring those chemists back on board again
So, we take those original scaffolds from the Waksman platform and the modify them to improve targeting,
stability, cell penetration, reduce resistance and side effects
The scaffolds that we get from nature are really hard for a drug company to get a patent on
A patent is what protects them from other companies using the same scaffold for their drug discovery
programs
So, if a drug company wants to protect a scaffold or molecule and that no one else can use it they require these
patents and to get a patent they have to show an inventive step where they have changed that molecule in
some way
Antibiotic creation by synthesis
We started off using scaffolds from nature and worked on a modification process where we are synthesizing
part of the molecule from the original scaffold
But we then moved across to creating antibiotics completely from synthesis
Where we don’t need to start with a base molecule, we just make them ourselves
Some antibiotics also come from other drugs in the market. Sometime the byproducts of certain drugs also
have antibiotic properties, so scientists run with that also
Drug discovery
1st antibiotics
The first antimicrobial called aniline came about in the 1850s
This was an reaction between nitrobenzene, iron and hydrochloric acid
Then in 1859 atoxyl came around by reacting aniline with arsenic
1st attempts at discovery
Friedrich Bayer company explored antibacterial activity of azo dye derivatives in the 1920s
Prontosil was then identified and commercialized in 1935
From this base drug prontosil they made over 5000 derivatives of this base compound, and we call these
sulfadrugs
1st screening platform
What people find interesting about this accidental discovery is that microbes were competing against each
other and producing compounds that we might find useful
Before this accidental discovery medicine was solely a chemistry perspective. So this accidental discovery This
opened up the idea that there will be a range of compounds out in nature and perhaps produces by different
microbes that we could utilize to target the microbes ourselves.
So, this set up the first screening platform called the Waksman platform
What Waksman discovered was that soil bacteria can inhibit growth of other bacteria
So, he made this platform to screen huge number of organisms for their compounds at once and see what
those compounds were
Antibiotic expansion by semi-synthesis
When we found each of these classes through these screening protocols, we could then take those antibiotics
and bring those chemists back on board again
So, we take those original scaffolds from the Waksman platform and the modify them to improve targeting,
stability, cell penetration, reduce resistance and side effects
The scaffolds that we get from nature are really hard for a drug company to get a patent on
A patent is what protects them from other companies using the same scaffold for their drug discovery
programs
So, if a drug company wants to protect a scaffold or molecule and that no one else can use it they require these
patents and to get a patent they have to show an inventive step where they have changed that molecule in
some way
Antibiotic creation by synthesis
We started off using scaffolds from nature and worked on a modification process where we are synthesizing
part of the molecule from the original scaffold
But we then moved across to creating antibiotics completely from synthesis
Where we don’t need to start with a base molecule, we just make them ourselves
Some antibiotics also come from other drugs in the market. Sometime the byproducts of certain drugs also
have antibiotic properties, so scientists run with that also
