Med Chem of Alkylating and Metallating Agents (Dr. Parang)

what are the drugs for nitrogen mustards ?

Mechlorethamine

Chorambucil

Melphalan

Cyclophosphamide

Ifosfamide

What are the drugs for DNA Methylators?

Temozolamide

Dacarbazine

Procarbazine

What are the drugs for Nitrosureas?

carmustine

lomustine

what is the drug for alkylsulfonates

busulan

the nucleophilic groups on DNA bases such as N7 of guanine readily attack the electrophilic drug

DNA cross linking agents

is DNA cross linking reversible or irreversible alkylation?

irreversible alkylation

alkylating agents form covalent bond to what in DNA

nucleophilic groups

alkylation of nucleic acid bases can result in what

miscoding

in nitrogen mustards and aziridine mediated alkylators the two chlorine atoms decrease the basic strength of amino acids nitrogen through a negative effect (t/f)

true

nitrogen mustards and aziridine mediated alkylators are

unionized conjugate

different classes of nitrogen mustards can be what

aliphatic or aromatic

aliphatic nitrogen mustards contain aliphatic nitrogen substituent (t/f)

true

what is the drug for aliphatic. nitrogen mustard that is IV administration

mechlorethamine

mechlorethamine is inactivated by what

sodium thiosulfate

non-toxic prodrug

lowered GI toxicity and less nonspecific toxicity

produced acrolein

what drug?

cyclophosphamide

sulfhydryl alkylation by acrolein and using mesna to reduce toxicity is what drug

Mesna

when is mesna used

to reduce risk of hemorrhagic cystitis associated with high dose ifosfamide or cyclophosphamide

what is oral administration and attenuate the severity of side effects

slows the rate of intramolecular nucleophilic attack

aromatic nitrogen mustards

what are the 3 drugs for aromatic mustard

chlorambucil

melphalan

uracil mustard

less reactive alkylating agent

less side reactions and less toxic

what class?

(Chlroambucil) aromatic mustard

teriary aziridine Is what drug

thiotepa

alykating agents causes interstrand cross linking in what

nitrosoureas

decompose in the body to form an alkylating agent and carbomulating agent is what class

nitrosourea

prodrug activated by demethylation in the liver is what drug

darcarbazine

prodrug activated In the body to form an alkylating agent is what drug

mitomycin C

alkyl sulfonate is what drug

busulfan

before reacting with DNA, the electron donating ligands (chloride) are displace through nucleophilic attack by cellular water is MOA of what

organoplatinum complexes

cisplatin forms intra-strand adduct that interferes with DNA functions and may not be adequately repaired (t/f)

true

hydrated platinum analogs are readily attacked by DNA nucleophiles (N7 of adjacent guanine residues)

true

prodrug that is neutral inactive molecule

high nephrotoxic

cisplatin

prodrug is covered by membrane bound AP to active thiol with free SH group is what drug

amifostine

what are the cisplatin analogues

carboplatin

oxaliplatin

Picoplatin

carboplatin is advantageous in the lack of renal toxicity evident with cisplatin (t/f)

true

oxaliplatin loses oxalate dianion in vivo to form the mono- and dehydrated diaminocyclohexane platinum analogs (t/f)

true

name of this is derived from the 2-methylpuridine (pico line) ring associated with the platinum atom

picoplatin

what reacts with DNA forming an intrstand cross link

oxaliplatin

which class involves formation of covalent DNA crosslinking

alkylating

Which one of these nitorgen mustards is more reactive?

Mechlorethamine

Chlorambucil

Cyclophosphamide

Melphalan

A

Which one of these compounds is a nitrosourea anticancer agent?

A

B

C

D

B

antineoplastic effect through the O6 methylation of guanine nucleotide is what

DNA methylators

prodrug activated by demethylation in the liver is what drug

dacarbazine

decomposes to form a methylidiazonium ion is what drug

dacarbazine

prodrug activated in the body to form an alkylating agent is what drug

mitomycin C

classified as an alkyl sulfonate

one of both of the methylsulfonate ester moieties can be displaced by the nucleophilic guanine, leading to monoalkylatted and cross linked DNA

busulfan

before reacting with DNA, the electron donating ligands (chloride) are displaced through nucleophilic attack by cellular water is what

organoplatinum complexes

intrastrand cross linking happens where ?

organoplatinum complexes

what forms intra strand adduct that interferes with DNA function and may not be adequately repaired

cisplatin

Please select the alkylating agent among the following structures.

You can respond once

Compound A

Compound B

Compound C

Compound D

C

hydrated platinum platinum analogs are readily attacked by DNA nucleophiles (N7 of adjacent guanine residues) due to net positive charge that has been regained on the Pt atom

organoplatinum complexes

highly nephrotoxic is what drug

cisplatin

electron deficient metal

two DNA nucleophiles

oragnoplatinum complexes

carboplatin is advantageous in the lack of renal toxicity evident with cisplatin (t/f)

true

what loses oxalate dianion in vivo to form the mono-and dehydrated diaminocyclohexane platinum analogs

oxaliplatin

the name of the antineoplatic is derived from the 2 methyl pyridine (pico line) ring associated with platinum atom

picoplatin

what forms the cytotoxic hydrated intermediate as cisplatin but does so at 10 fold slower rate, making it 20 to 40 fold less potent chemotherapeutic agents

carboplatin

what is less mutagenic, nephrotoxic, hematotoxic, and ototoxic than cisplatin

oxaliplatin

Te mechanism of action of ----------involves the formation of covalent DNA crosslinks.

Carboplatin

Cytarabine

Methotrexate

6-Mercaptopurine

A

Which statement is true?

Cisplatin loses oxalate in vivo to form the mono- and dihydrate platinum analogs.

Carboplatin loses oxalate in vivo to form the mono- and dihydrate platinum analogs.

Oxaliplatin loses oxalate in vivo to form the mono- and dihydrate platinum analogs.

Picoplatin loses oxalate in vivo to form the mono- and dihydrate platinum analogs.

C

what is associated with a higher risk of nephrotoxicity

Cisplatin