DnD: Infectious Medchem

Who discovered arsphenamine?

Ehrlich

Who discovered sulfa drugs?

Bayer

Who discovered penicillin?

Fleming

Sulfonamides are ____ compounds.

synthetic organic

Quinolones are ____ compounds.

pure synthetic

Macrolides and ketolides are ____ compounds.

large cyclic

Peptides are ____ compounds.

naturally derived

Sulfa drugs are ____ and ____ antibiotics.

bacteriostatic

broad spectrum

Sulfonamides mimic the structure of ____.

PABA

The N4 amine undergoes ____ and ____ metabolism to form ____ compounds.

acetylation

glucuronidation

inactive

The two metabolites of prontosil are ____ and ____.

sulfanilamide (antibacterial)
poly aminobenzene (carcinogenic)

Prontosil is a ____ that undergoes ____ to form ____.

prodrug

reduction

sulfonilamide

SAR of sulfonamides:

N4 must be free (unsubstituted) or potentially free (azo, nitro, hydroxyl, nitrosyl, or amide).

N4 must be in the para position.

The aromatic ring must be a benzene and the benzene must be unsubstituted.

N1 substitution is allowed. Electron withdrawing substituents are preferred because they increase activity and water solubility (pKa= 6.6-7.4)

Which enzyme is inhibited by sulfonamides?

Dihydropteroate synthase, which is crucial for folate synthesis in bacteria.

What are the two mechanisms of action of sulfonamides?

competitive inhibition of dihydropteroate synthase

the formation of a false metabolite

Explain the synthesis of bacterial DNA.

Dihydropteroate diphosphate combines with PABA to via the enzyme dihydropteroate synthase to form dihydropteroic acid. Dihydropteroic acid becomes tetrahydrofolic acid via the enzyme folate reductase. Tetrahydrofolic acid is then converted into thymidine and then to DNA.

What enzyme does trimethoprim inhibit?

folate reductase.

Which sulfonamides are short/medium acting?

sulfisoxazole

sulfacetamide

sulfamethoxazole

sulfadiazine

Which sulfonamides are long acting?

sulfamerazine

sulfalene

Is mafenide considered a sulfa drug? why or why not?

Mafenide is not a sulfa drug. Although it resembles the structure of a sulfa drug, it is not one because the N4 NH2 is not directly attached to the benzene ring. It is separated by CH2. Mafenide is not active (in terms of exam questions).

What is the mechanism of action of trimethoprim?

Trimethoprim’s diaminopyrimidine inhibits microbial dihydrofolate reductase.

Which N4 substituent(s) is/are reduction dependent?

azo (NN)

nitro (NO2)

hydroxyl (NHOH)

nitrosyl (NO)

Which N4 substituent(s) is/are hydrolysis dependent?

amide (CONH)