Lecture 3 Non-covalent bonding drugs Flashcards Preview

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Flashcards in Lecture 3 Non-covalent bonding drugs Deck (17)
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1
Q

noncovalent binding drugs

A

anthracyclines**

other abx

2
Q

Anthracyclines

A
  • produced by streptomyces peucetius bacteria
  • minor structural modifications = wide change in activity
  • wide range of compounds have been screened
  • 7 are in clinical use
3
Q

Daunorubicin/daunomycin

A

isolated from Streptomyces
use limited to induction tx of acute leukemia
- use at high dose for induction - to destroy malignant cells and induce healthy cell growth

4
Q

Doxorubicin/adriamycin

A

isolated from mutated strain of same fungus (streptomyces). More effective in tx of solid tumors. Most widely used

5
Q

semisynthetic anthracyclines

A

Epirubicin - stereoisomer of doxorubicin. More lipophilic

Idarubicin - primarily for acute leukemia - replaced daunorubicin

6
Q

MOA of rubicins

A
  1. DNA intercalation
  2. ROS formation
  3. Topoisomerase II inhibition
    inhibits DNA and RNA synthesis
    Cell cycle non-specific
7
Q

DNA intercalation

A

planar drugs intercalate between the DNA bases = DNA breakage
Blocks DNA synthesis and transcription

8
Q

Reactive Oxygen Species

A

not a single species
Oxygen free radicals, hydrogen peroxide, hydroxyl radicals
bind to DNA/RNA protein and damage, as well as damage to proteins and lipids in both tumor and normal cells

9
Q

ROS SE

A
cardiac toxicity
free radicals (lipid peroxidation) may damage heart muscle 
hard to predict
oncologists monitor carefully.
may survive chemo, but die from SE
10
Q

Topoisomerase II inhibition

A

Breaks and re-ligates double-strand DNA for transcription and replication
break strand = inhibit synthesis and replication
usually cell-cycle S-phase sensitive

11
Q

Resistance to anthracyclines

A

enter cell via passive diffusion = high intracellular concentration

  1. substrate for Pgp efflux pump
  2. drug resistance results from mutations in topoisomerase II
12
Q

Daunorubicin toxicity

A

cardiotoxicity, alopecia, and bone marrow depression

13
Q

Doxorubicin

A

cardiotoxicity, alopecia, bone marrow depression, and stomatitis

14
Q

Idarubicin

A

cardiotoxicity, mucositis, and bone marrow depression

15
Q

Bleomycin

A

isolated from steptococcus verticillus
small peptide with a DNA-binding region (intercalation) and an iron-binding region (free-radical)
similar to anthrocyclines

16
Q

Bleomycin MOA

A
  1. DNA intercalation = DNA breakage

2. Hydroxyl free radicals formation = DNA breakage (complex with divalent cation, such as iron)

17
Q

Bleomycin toxicity

A
  1. minor myelosuppression
  2. pulmonary fibrosis = only drug that does this
  3. toxicities do not overlap with other drugs
  4. important in combo tx