pyrimidine purine antineoplastics Flashcards
Leflunomide
disrupts carbomyl phosphate –> orotic acid step in purine synthesis
Hydroxyurea
disrupts UDP –> dUDP step in purine synthesis via ribonucleotide reductase inhibition
5-FU
disrupts the dUMP–> dTMP via THF(methylene)–> DHF step via inhibition of thymidylate synthesis
MTX
disrupts DHF –> THF via dihydrofolate reductase
TMP
disrupts DHF –> THF via dihydrofolate reductase
pyrimethamine
disrupts DHF –> THF via dihydrofolate reductase
6-MP
disrupts PRPP–>IMP
Mycophenolate, ribarvirin
disrupts IMP–> GMP
Pyrimidine synthesis disrupters
Leflunomide, MTX, TMP, pyrimethamine, 5-FU
Purine synthesis disrupters
6-MP
mycophenolate, ribavirin
inhibits dihydroorotate dehydrogenase
leflunomide
inhibits dihydrofolate reductase in humans, bacteria, and protozoa respectively
- MTX - humans
- TMP - bacteria
- pyrimethamine - protozoa
prodrug is azathioprine
6-mercaptopurine, inhibits de novo purine synthesis
inhibit inosine monophosphate dehydrogenase
mycophenolate and ribovirin
inhibits ribonucleotide reductase
hydroxyurea
de novo pyrimidine synthesis requires what amino acids?
aspartate
de novo purine synthesis requires what aa?
aspartate, glycine, glutamine, and THF
capecitabine
prodrug form of 5-FU
structural analog of para-aminobenzoic acid
sulfonamides
what do sulfonamides accomplish?
they inhibit folic acid production in bacteria; humans do not synthesize folic acid and must get it from vitamines
reversible inhibitor of inosine monophosphate dehydrogenase
mycophenolic acid: prevents IMP–> xanthine monophosphate
drug deprives rapidly proliferating B and T cells of key components of nucleic acids. drug is a immunosuppressant used to prevent graft rejection.
carbomyl phosphate synthetase
I and II
CPS1: m1tochondria (urea cycle)
CPS2: cyTWOsol (de novo pyrimidine synthesis)
