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Chemotherapy Drugs (modes of action) I

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Learning objectives:
- Understand the relationship between DNA structure and modes of intercalation
- Have an insight into the therapeutic mode of action of Doxorubicin
- Know the sites of alkylation in DNA
- Describe DNA alkylation with chlorambucil and cyclophosphamide

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biology chemistry medicine Edad recomendada: 18 años
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Zainab Nabeel
Zainab Nabeel
Bahréin

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Chemotherapy Drugs (modes of action) I

Learning objectives: - Understand the relationship between DNA structure and modes of intercalation - Have an insight into the therapeutic mode of action of Doxorubicin - Know the sites of alkylation in DNA - Describe DNA alkylation with chlorambucil and cyclophosphamide

Zainab Nabeel
1

Doxorubicin adenine planar bacteria cytosine Electrostatic

Understand the relationship between DNA structure and modes of intercalation

Intercalating agents :
Intercalating drugs contain a aromatic or hetero - aromatic ring system which can fit into the double helix of DNA and distort its structure . Once bound , the drug can inhibit the enzymes involved in replication and transcription processes . Anthracyclines are a set of naturally occurring antibiotics isolated from which have anti - cancer properties
with a mode of action involving DNA intercalation .

Have an insight into the therapeutic mode of action of Doxorubicin

is an Anthracycline which intercalates DNA . During replication
Doxorubicin interferes with the activity of the DNA - topoisomerase II complex which cuts and reseals DNA to relieve tension during uncoiling .
DNA often remains cut . This prevents DNA replication and prevents cell replication . It usually causes cell death .

Doxorubicin :
- Isolated from streptomyces peucetius in1967
- One of the most effective anti - cancer agents ,
used to treat a broad spectrum of solid tumors
- Intercalates into DNA and acts as a topoisomerase II ( an enzyme involved in DNA replication process ) poison as it stabilizes the complex formed between DNA and topoisomerase II
- Excessive number of stabilized DNA - enzyme complexes
triggers apoptosis

Doxorubicin Bound to DNA :
Inserts at GC and CG base pairs causing a 'buckle'
- prevent van der Waals contacts between NBs .
- distort DNA structure
Stabilized by
- interaction ( - NH3 + amino sugar with phosphate )
- H - bonding
- Aromatic pi - pi interactions

Know the sites of alkylation in DNA

N7 of guanine , N1 , N3 , and N7 of , and N3 of .

Describe DNA alkylation with chlorambucil and cyclophosphamide

It is explained somewhere else

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