PHARMACY, CHEMISTRY, MEDICINAL CHEMICTRY, ANTIMETABOLITES & 6- THIOGUANINEANTICANCER DRUGS MECHANISM OF ACTION CLASSIFICATION ANTIMETABOLITES METHOTREXATE 5 – FLOROURACIL 6 – MERCAPTOPURINE

1. Presented by :
Miss Harshita singhai
B. Pharm sem. 7
ANTIMETABOLITES & 6- THIOGUANINE
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2. CONTENTS
 ANTICANCER DRUGS
 MECHANISM OF ACTION
 CLASSIFICATION
 ANTIMETABOLITES
 METHOTREXATE
 5 – FLOROURACIL
 6 – MERCAPTOPURINE
 6- THIOGUANINE {MOA , SAR,
SIDE EFFECTS, METABOLISM}
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3. ANTICANCER DRUG
Anticancer drug, also called antineoplastic drug, any drug that is
effective in the treatment of malignant, or cancerous, disease. There
are several major classes of anticancer drugs; these include alkylating
agents, antimetabolites, natural products, and hormones. In addition,
there are a number of drugs that do not fall within those classes but
that demonstrate anticancer activity and thus are used in the treatment
of malignant disease. The term chemotherapy frequently is equated
with the use of anticancer drugs, although it more accurately refers to
the use of chemical compounds to treat disease generally.
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4. CELL CYCLE SPECIFIC/NON-SPECIFIC DRUGS
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5. MOA OF ANTICANCER DRUGS
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6. 6

7. ANTIMETABOLITES
Antimetabolites are called a “cytotoxic” type of drug because they kill
cells. They work by mimicking the molecules that a cell needs to
grow. Cells are tricked into taking in the drugs and then using the
antimetabolites instead of their normal building blocks of genetic
material: RNA and DNA. With the drugs on board, the cells can no
longer copy their DNA, so they can’t divide into new cells. Because
antimetabolites target cells only as they are dividing, these
medications are most effective against tumors that are growing
quickly.
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8. Methotrexate
• Methotrexate potently inhibits
DIHYDROFOLATE
REDUCTASE{DHFR}
• This leads to decreased
prodution of compounds
adenine,guanine and thymidine
and the amino acids methonine
and serine,depletion of
thymidine.as a result DNA,
RNA and protein synthesis are
depressed and finally cell
death.
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9. 5 FLUOROURACIL{5 FU}
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10. 6 - MERCAPTOPURINE {6 MP}
6MP are converted in the body to the corresponding
monoribonucleotides which inhibits the conversion of inosine
monophosphate to guanine and adenine nucleotides.There is also
feedback inhibition of De Nevo Purine synthesis. 10

11. 6- THIOGUANINE {6-TG}
The 6-thioguanines are the anti metabolites that interfere with purine
nucleotide synthesis within the cell cycle, and they thereby impair
proliferation of rapidly dividing T and B lymphocytes.
6-Thioguanine (Thioguanine; 2-Amino-6-purinethiol) is an anti-
leukemia and immunosuppressant agent, acts as an inhibitor of SARS
and MERS coronavirus papain-like
proteases (PLpros) and also potently
inhibits USP2 activity, with IC50s of
25 μM and 40 μM for Plpros and
recombinant human USP2, respectively.
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12. MOA OF 6-THIOGUANINE
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13. Structural Activity Relationship of 6 TG
• The activity of the drug increases with increase in the carbon
chain upto 15-16 carbons, after that, it again decreases.
• Substituent at position 6 which can lead to the increase in the
resonance at 6th position will lead to increase in the activity of
the drug.
• Introduction of the hydrophobic substituent at 6th position will
increase the activity of the drug.
• Substitutions at 2nd position may not change the activity of the
drug, or it may decrease the activity of the drug depending upon
the type of substituent.
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14. Side Effects
• Low bloodcounts and liver toxicity are common side effects of
this drug.
• Other side effects can be nausea, loss of appetites, infertility
and some liver problems.
• Some of the uncommon side effects includes tumor lysis
syndrome and vino-occlusive liver disease
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15. METABOLISM OF 6 - TG
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17. REFERENCES
BEALE J.M., BLOK J.H., “WILSON AND GISVOLD’S TEXTBOOK OF
ORGANIC MEDICINAL AND PHARMACEUTICAL CHEMISTRY”. ED-12,
WOLTERS KLUMER,PG.NO.: 372-380.
TRIPATHI K.D. ,“ESSENTIALS OF MEDICAL PHARMACOLOY,” EDITION= 5,
2003, JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD, NEW DELHI,
PG.NO.: 987.
ALAGARSAMY V.“TEXTBOOK OF MEDICINAL CHEMISTRY ” VOL-
2,ELSEVIER PUBLICATION, PG. NO. 455.
ANTICANCER DRUG THERAPY {CHEMOTHERAPY &
OTHERCANCERCARE.MB.CA/TREATMENTS.
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18. THANK YOU
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