21 - sulfa drugs Flashcards
what are antibiotics
“anti-life”, selective poisons for microbes. had the second largest impact on human life
what are the drugs targeted towards bacteria, viruses, fungi
- Bacteria = anti biotics
- Viruses = anti viral
- Fungi = anti fungal
- Protozoa
what is the leading cause of death through history
infectious disease
who invented the magic bullet and in what year
paul erlich, 1907
explain the trypan red and trypanosomes example
- paul noticed that there was a red dye that worked well against trypanosomes
- trypanosomes is the infectious agent of african sleeping sickness, spread by the titsee fly
- noticed that some of the trypanosomes would soak up the red dye and that would give them a selective colour (the dye selectively enters the cells of the trypanosomes but it doesnt enter the rbcs very well)
- paul says okay i can make a drug that is selective and only targets trypanosomes but not other important cells like RBC
what drug did elrich make? what techniques did he use to do it?
- Salvarsan 606 (first ever antibiotic)
- he used trypan red as a lead → did SAR to see if he could change his dye into a drug
- in the trypan atom there are two N atoms, so he decided to change these into As
- As is chemically similar to N, but it is toxic, so he thought it would have selectivity to go and kill the trypanosomes
what was the success of salvarsan 606? what were the benefits of it? what were the issues with it?
- poor product
- worked at treating syphilis
- was not drug like
- Drug very insoluble (technical problem, have to use a dilute solution)
- 600 mL each injection (extremely large size for drug)
- Required 1 hour with a syringe
- if the needle did not enter the vein, it would cause necrosis (leading to amputation)
explain the importance of prontosil
- gerhard domagk found a dye called prontosil was good at clearing infections in mice
- cured his daughters throat infection with it, proving it could be used as an antibiotic
- only effective in vivo
why is prontosil effective?
- prontosil requires metabolism to work
- when it passes through the liver, it gets cut in half, making sulfanilamide (active ingredient)
- prontosil is a pro drug, sulfanilamide is a drug
what is the mechanism of action of sulfanilamide
- it interferes with growth, does not kill bacteria
- patient requires a good immune system
- sulfanilamide interferes with coenzyme F
how do sulfa drugs inhibit the synthesis coenzyme F?
- dihydropteroate synthase = enzyme that brings two materials together
- intermediate is made during SN2 reaction
- intermediate turns into coenzyme F
- sulfa drugs block the action of the enzyme = no immediate structure formed = no coenzyme F formed
explain how sulfa drugs are competitive inhibitors
- sulfonamides compete with PABA for the active side on the enzyme
- PABA cannot bind to the substrate
explain the similarities in structure between PABA and sulfanilamide
- sulfanilamide has a structure that resembles that of PABA
- both molecules can bind to the active site in the same way (this is why sulfanilamide is such a good competitive inhibitor)
- both have same pattern of bonding (H bond, van der waals, ionic bond)
explain the strategy for competitive inhbition for sulfa drugs
- sulfa is inhibitor and binds to the enzyme
- enzyme is not able to function and cannot make coenzyme F
- sulfa drug makes the EI complex (reduces the amount of free enzyme available to conduct the reaction)
explain the selectivity of sulfanilamide and why is is a good competitive inhibitor
- sulfanilamide only exists in bacteria, so it will only target bacteria, not any human cells
- sulfanilamide is better at binding to the enzyme than PABA
