Antimicrobial chemotherapy

Question 1

Describe the work of Ehrlich:

Answer 1

developed the fist antibacterial chemotherapy drug (Salvarsan - Arsephenamine) which was supposed to treat morning sickness but was toxic as it caused blindness. So the drug was used as a lead and was optimised to produce Salvarsan which was compound number 606. This treated syphilis (an STI)

Question 2

What was developed after Salvarsan and why?

Answer 2

Neosalvarsan - this was used to treat syphilis (until the introduction of penicillin) because it was more water soluble and less toxic than salvarsan

Question 3

What is the mechanism of action of Salvarsan?

Answer 3

It is a pro-drug which is metabolised to oxophenarsine (Mapharsen) which reacts with thiol groups in proteins, causing denaturation.

Question 4

What were Ehrlichs contributions to chemotherapy?

Answer 4

• He recognised the importance of selective toxicity (therapeutic index)
• screening techniques
• structure activity relationships
• pro-drugs (drug activation by metabolism)