Professional Documents
Culture Documents
Classes:
1. Pyrimidine Analogues - 6-membered
ring consisting of four carbon atoms and
two nitrogen centers at the 1- and 3ring positions
2. Purine Analogues - purine is a
heterocyclic aromatic organic
compound. It consists of a pyrimidine
ring fused to an imidazole ring
Characteristics:
closely related in structure to a
cellular precursor molecule
prevent the biosynthesis of
normal cellular metabolites
S-phase-specific
Myelosuppression is the dose
toxicity for all drugs in this class
CELL CYCLE/ CELL DIVISION
3. Folates - a general term for a group of
water soluble b-vitamins, and is also
known as B9; compounds designed to
interact at cofactor sites for enzymes
involved in the biosynthesis of nucleic
acid bases
PURINE ANTIMETABOLITES
6-Mercaptopurine:
- inhibition of purine biosynthesis
- thiol analog of hypoxanthine
- should be activated to as
ribonucleoside, 6-thioinosate
6-Mercaptopurine
(prodrug)
HGPRT
(enzyme)
Allopurinol:
potent inhibitor of XO (xanthine oxidase)
6-thioinosate
a.) S-methylation
6-MP
thiopurine 5-methyl-transferase
(TPMT)
S-methyl MP
b.) oxidation
6-MP xanthine oxidase thiouric acid
- used as an adjuvant
- increases both potency and toxicity of 6-MP
- prevents uric acid kidney toxicity
Heterocyclic derivatives of 6Mercaptopurine: (for protection from catabolic reactions)
a.) Azathioprine
- less effective than 6-MP
- important role as IMMUNOSUPPRESSIVE
AGENT in organ transplants
b.) Vidarabine
- adenosine arabinoside
D-arabinose (sugar moiety):
-competitive inhibitor of DNA polymerase
- for antineoplastic and antiviral activity
-limited to antitumor effect by susceptibility to
adenosine deaminase (adenosine deaminase- siya
PYRIMIDINE ANTIMETABOLITES
PYRIMIDINE DRUGS
*** Inactivation:
a.) Inactivation by dihydropyrimidine
dehydrogenase (DPD)
- -fluoro--alanine: major human metabolite
of 5-FU
Remedy:
- 5-FU is dosed with uracil and 5-FU prodrugs
- 5-chloro-2,4-dihydroxypyrimidine (CDHP)
inhibitor of DPD
*** Tegafur
-tetrahydrofuran derivative
-require high doses
-esters of N-hydroxymethyl derivative of tegafur
show greater anticancer activity
*** Cytosine Structures:
FOLATES
*** Methotrexate
-classic antimetabolite of folic acid
-inhibits binding of the substrate folic acid to the
enzyme dihydrofolate reductase (DHFR)
-resulting to reduction in synthesis of nucleic
acid bases, perhaps most importantly, the
conversion of uridylate to thymidylate as
catalyzed by TS
Side effect: bone marrow suppression,
pulmonary fibrosis, GI ulceration (pakitandaan salamat!)
Leucovorin is given 6-24 hours to prevent the
long term effects on normal cells by preventing
the inhibition of DNA synthesis
*** Pemetrexed
-inhibits DHFR, TS, and GARFT (Glycinamide
ribonucleotide formyl transferase
HYDROXYUREA
(structure yan ng folic acid)
(note: hindi siya kabilang dun sa tatlong classes, pero isa siyang antimetabolite..
kumbaga, unclassified antimetabolite??? :D)
Thankyou!! -chaz