Anticancer Agents: Part II

1. ANTINEOPLASTIC AGENTS
PART-II
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2. ANTINEOPLASTIC ANTIBIOTICS
 Bleomycin
 Doxorubicin
 Dactinomycin
 Daunorubicin
• Produce direct action on DNA.
• Interacts with DNA, leading to disruption of DNA function.
• Also Inhibit topoisomerases , inhibit RNA synthesis.
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3. Bleomycin
Obtained from Streptomyces verticillus
Mode of Action
It acts by forming DNA-bleomycin-Fe2+ complex which
undergoes oxidation to form DNA-bleomycin-Fe3+.
The liberated electron reacts with oxygen to form superoxide or
hydroxyl radical which then cut DNA causing chain
fragmentation and thus release of free base pairs.
It is mainly effective in
G2 phase of cell cycle.
Side effect: Myelosuppression 3

4. Doxorubicin and Daunorubicin
 Both are anthracycline derivatives.
 Obtained from Streptomyces peucetius
Mode of action
Act by inhibiting enzyme topoisomerase-II, a enzyme
responsible for DNA and RNA synthesis.
It generates quinone type free radical which is responsible for
its cytotoxic effect.
Side effects: Hair loss, Myelosuppression, rashes, GIT
disturbances
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Dactinomycin
Obtained from Streptomyces parvullus
Mode of action
Act by inhibiting enzyme Topoisomerase-I and Topoisomerase-II and
thus inhibit DNA and RNA synthesis.
It also inhibits enzyme RNA polmerase and thus interfere in transcription
also.

6. PLANT PRODUCTS
These are plant-derived substances .
The mitotic spindle apparatus is disrupted, and segregation of
chromosomes is arrested.
Vinca Alkaloids: Vincristine, Vinblastine
Etoposide from Podophyllum peltatum
Other natural antineoplastic agents include
 Taxanes
 Paclitaxel
 Docetaxel 6

7. VINCA ALKALOIDS
 Obtained from Catharanthus roseus/ Vinca rosea
 Isolated alkaloids include Vincristine, Vinblastine
 These drugs bind to tubulin and inhibits/prevents their
polymerization into microtubules and thus prevent spindle
formation during mitosis.
 Side effect: Myelotoxicity, Neurotoxicity
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8. ETOPOSIDE
 It is an semisynthetic derivative of podophyllotoxin derived from May apple,
Podophyllum peltatum.
 Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II
and DNA. This complex induces breaks double stranded DNA and prevents
repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry
into the mitotic phase of cell division, and lead to cell death. Etoposide acts
primarily in the G2 and S phases of the cell cycle.
 ADR: Alopecia, GIT disturbances,
Myelosuppression.
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9. TAXANES
 Obtained from Yew tree Taxus brevifolia.
 Their mode of action is opposite to Vinca alkaloids.
 They enhance polymerization and thus stabilize microtubules in
freeze state and thus inhibit cell division.
 Examples: Paclitaxel, Docetaxel
Camptothecan analogues
Obtained from enzyme Campotheca accuminata
Inhibit enyme Topoisomerase-I and thus prevents reannealing of
DNA strand.
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10. MISCALLANEOUS
Cisplatin
 First anticancer Compound containing Platinum.
 Pt forms complex with DNA, cause crosslinking, thus interfere
with DNA repair mechanisms, causing DNA damage, and
subsequently inducing apoptosis in cancer cells.
 Due to undesirable side effects such as severe kidney
problems, allergic reactions, gastrointestinal disorders,
hemorrhage, and hearing loss especially in younger patients,
other platinum-containing anti-cancer drugs such as carboplatin,
oxaliplatin etc, have also been used. 10

11. MITOTANE
 Adrenal cortex cell inhibitor so used in treatment of
adrenocortical tumors.
 It mainly inhibit the enzymes involved in steroid
biosynthesis.
 Structure resembles to DDT but not harmful to humans.
 Side effects include Anorexia, Nausea, Diarrohea, Rashes
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