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Med Chem Exam 5 - Antitumor Antibiotics

Terms in this set (73)

___________ agents are "flat compounds" that bind strongly to DNA by slipping between two sets of base pairs in the double helix
Intercalating
Intercalating agents inhibit ___________.
topoisomerase
Intercalating agent produced by streptomyces parvulus
Dactinomycin
Which intercalating agent has a peptide-lactone system?
Dactinomycin
Dactinomycin's (lactone/tricyclic) component inserts into the (major/minor) groove of DNA.
tricyclic, minor
At high doses, dactinomycin inhibits all but:

a. RNA synthesis
b. protein synthesis
c. DNA synthesis
d. folylpolyglutamyl synthetase
e. topoisomerase
d
Inhibition of RNA synthesis requires much (higher/lower) dactinomycin concentration than that for inhibition of DNA synthesis
lower
The _______ moiety of some intercalating agents produces reactive oxygen species
quinone
...
doxorubicin
The (sugar/anthraquinone) moiety of doxorubicin and daunorubicin produces oxygen free radicals; these can be severely cardiotoxic
anthraquinone
The (sugar/anthraquinone) moiety of doxorubicin and daunorubicin intercalate into DNA base pairs
anthraquinone
The anthraquinone moiety of doxorubicin and daunorubicin intercalate into DNA base pairs in the (major/minor) groove
major
Doxorubicin and daunorubicin produce DNA single strand breaks and inhibit repair. Which of the following is NOT a theory of their mechanism of action?

a. they produce free radicals

b. they inhibit dihydrofolate reductase

c. they "nick" DNA

d. they inhibit topoisomerase II
b
The two anthracycline intercalating agents are ___________ and __________.
doxorubicin, daunorubicin
CYP 450 Reductase and ______ shuttle a single electron between doxorubicin and oxygen during redox cycling.
NADPH
True or false: Mitoxantrone is less cardiotoxic than doxorubicin.
false
...
mitoxantrone
What drug in this unit causes a delayed transit through the S-phase?
etoposide
True or false: Mitoxantrone is an intercalating agent and inhibits topoisomerase II
True
...
etoposide
True or false: Etoposide is an intercalating agent
False
Cells are most sensitive to etoposide in what phases?
S, G2
Etoposide is thought to work inhibiting topoisomerase II and also by blocking the proper functioning of the:

a. mitochondria

b. ribosomes

c. Golgi apparatus

d. Na+/K+ ATPases
a
What enzymes manage the configuration of the DNA helix?
topoisomerases
A group of glycoproteins produced by streptomyces verticillius
Bleomycins
Bleomycins are administered as a mix of all but which of the following:

a. bleomycin B1-4

b. bleomycin A2

c. bleomycin AI2

d. bleomycin C8
d
Iron +2 is oxidized to Iron +3 in the mechanism of which drug?
bleomycin
The bleomycins transfer an electron from
Fe++ to O2 to produce __________.
superoxide
Which of the following produces superoxide?

a. doxorubicin

b. mitomycin C

c. daunorubicin

d. bleomycins

e. they all produce superoxide
e
Bleomycin is most toxic in which tissues?
skin, lungs
______ are much more effective at inhibiting DNA synthesis than RNA synthesis. They also cause cells to accumulate in the G2 phase.
Bleomycins
True or false: Bleomycins cause strand scission and fragmentation of DNA -- both single and double strand breaks.
True

(scission is a fancy word for "breakage" as far as I can tell)
Bleomycin is contraindicated in patients over 50 with _______ disease
pulmonary
Produced by streotomyces caespitosus; a bifunctional molecule that can crosslink AND form damaging free radicals
Mitomycin C
True or False: Mitomycin can form crosslinks
true
...
Mitomycin C
Which of the following is not one of the functional groups in mitomycin that causes cell damage?

a. Perhalo ketone

b. Urethane

c. Aziridine

d. Quinone
a
Mitomycin C generates free radicals when it is reduced from the quinone to the ___________.
hydroquinone
True or false: Mitomycin is a prodrug
true

(it has to get reduced to the hydroquinone to be active)
The molecule on the (left/right) is the hydroquinone form of mitomycin
right
The molecule on the (left/right) is hydroquinone
left
The molecule on the (left/right) is the quinone
right
Mitomycin forms crosslinks by bonding with the O6 and N2 of guanine and N6 of ______.
adenine
DNA attacks the (aziridinium/hydroquinone) ion in Mitomycin
aziridinium
2 drugs derived from a periwinkle plant
vincristine, vinblastine
__________ and ________ cause dissolution of spindles during metaphase
vincristine, vinblastine
Vincristine and vinblastine cause dissolution of the spindles during _________.
metaphase
Vincristine, vinblastine, and paclitaxol stop cell division at ____phase.
meta
Vincristine and vinblastine (promote/inhibit) the polymerization of tubulin molecules
inhibit
Comes from a yew tree
paclitaxel
Paclitaxel is also known as
Taxol
Paclitaxel side chain at C__ is essential for activity
13
(Docletaxil/paclitaxel) is more potent
Docletaxil
Paclitaxel promotes microtubule (formation/dissolution)
formation
...
paclitaxel
Vincristine & vinblastine promote microtubule (formation/dissolution)
dissolution
Paclitaxel prevents microtubule (formation/disassembly)
disassembly
paclitaxel resistance is due to cells making (more/less) p-glycoproteins
more

(p-glycoproteins force harmful molecules out of cells)
What forms covalent bonds with DNA but is not an alkylating agent?
cisplatin
...
cisplatin
If cisplatin is dissolved in water, the equilibrium shifts to the (left/right)
right
If cisplatin is dissolved in sea water, the equilibrium shifts to the (left/right)
left
Hydrolysis is (faster/slower) in D5W than in normal saline.
faster
True or false: Cisplatin will bind to all bases, but most strongly with adenine
False

(guanine)
Pick the best solvent for cisplatin (assuming you want it to have the highest cytotoxicity possible):

1. 0.9% NaCl in water

2. 1/2 normal saline

3. Bacteriostatic H2O

4. D5W
1
_________ tumors are most sensitive to cisplatin
testicular
Cisplatin forms (inter/intra)strand crosslinks
intra
antitumor agents that cause dissolution of the spindles (microtubles), stopping cell division at metaphase (cytostatic)
vincristine, vinblastine
vincristine and vinblastine are indole alkaloids isolated from
"Catharantus roseus" (periwinkle) aka Vinca rosa
antitumor agent isolated from the bark of "Taxus brevifolia," aka Western yew or Pacific yew
paclitaxel (Taxol)
indole
present in vinca alkaloids: vincristine, vinblastine
cisplatin is the most stable in which solution:

D5W
1/2NS
NS
NS

-most stable in NS because the Cl- pushes the equilibrium to the left (as opposed to the hydrated form)

rank stability:
(D5W < 1/2NS < NS)
Organoplatinim complex that binds to DNA as a bidentate complex. Will bind to all bases, but most strongly with guanine
cisplatin
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