Nucleotide drugs

Question 1

Allopurinol

Answer 1

For gout

hypoxanthine analog -xanthine oxidase> alloxanthine

• > binds irreversibly to enzyme (inhibits)
• > dec uric acid production

Hypoxanthine, xanthine -HGPRT> IMP, XMP

• > inhibit PRPP synthetase and PRPP-amido-trans
• > dec purine biosynthesis

Question 2

Methotrexate

Answer 2

For osteogenic sarcoma, chronic inflammatory

Binds to dihydrofolate reductase
-> depletes THF -> depletes purine and pyrimidine pools

Toxic to all rapidly dividing cells (marrow, hair, skin)
Rescue with THF
- could also rescue cells with hypoxanthine and thymidine

Question 3

Sulfanilamide

Answer 3

Antibacterial

Analog of p-aminobenzoic acid (PABA)
-> intermediate -> folic acid
Blocks folate production - specific to bacteria

Question 4

Trimethoprim

Answer 4

Antibiotic (parasite, bacterial with sulfanilamide)

Folate analog
Binds DHF reductase
tighter in micro-organisms than human DHFR

Question 5

Fluorouracil

Answer 5

Cancer chemo

Pyrimidine analog
-orotic phosphoribosyl trans> F-UMP -> F-UDP -> F-dUMP

F-dUMP binds/inhibits thymidylate synthase + THF
-> depletes thymidine pools

Question 6

Mercaptopurine

Answer 6

Cancer cytotoxic

Analog of hypoxanthine
6-mercaptopurine -HGPRT> nucleotide
-> inhibits PRPP amido-transferase -> depletes purines

Question 7

Cytosine arabinoside

Answer 7

Cancer

Ara-C -deoxycytidine kinase> Ara-CMP -> -> Ara-CTP
Incorporated -> terminates chain

Only targets cells with active deoxy-cytidine kinase

Question 8

Acycloguanosine

Answer 8

aka acyclovir
Antiviral (HSV)

-HSV thymidine kinase> acycloguanosine MP -» acycloTP
Incorporated -> terminates chain

Question 9

Azidothymidine

Answer 9

aka AZT aka zidovudine
Antiviral (HIV)

-> -> AZT-TP
-> inhibits HIV DNA polymerase (reverse transcriptase)
(HIV poly is 100x more sensitive than host cell)