25 Med Chem Cancer Chemotherapy

nitrosourea

Identify the pharmacophore

bis(beta-haloalkyl)amine pharmacophore of the

nitrogen mustards/aziridine-mediated alkylators

Identify the pharmacophore and class

bis(beta-haloalkyl)amine pharmacophore of the

nitrogen mustards/aziridine-mediated alkylators

Identify the pharmacophore and class

Nitrosurea

Identify the pharmacophore

DNA Methylator

-Note these all have 2 or 3 Nitrogens in a row

Identify the pharmacophore

Organoplatinum

Identify the class

Organoplatinum

Identify the class

Crosslinked guanines on an organoplatinum

-note platinum is the atom doing the crosslinking

what is this showing?

-pentacyclic lactone of the topoisomerase inhibitors

(specifically, camptothecin class, and this is irinotecan); lactone is at the C21

Identify the pharmacophore

-pentacyclic lactone of the topoisomerase inhibitors (specifically, camptothecin class, and this is topotecan)

Identify the pharmacophore

-glycoside (sugar) analog of podophyllotoxin. These are topoisomerase inhibitors

-also 5 rings like camptothecins (eg/ irinotecan), but the rings are non-contiguous

Identify the pharmacophore and class

9,10-anthraquinone

- seen in anti-neoplastic antibiotics

Identify the pharmacophore

-antineoplastic antibiotic (just like the topoisomerase ABX, just different structure and MOA)

Identify the class

Pyrimidine antagonist (note 5-fluorine)

Identify the class

Pyrimidine antagonist (note 5-fluorine)

Identify the class

-methotrexate, a folate antagonist

-competes w/ DHF for DHFR enzyme

Identify the class

-methotrexate, a folate antagonist

-competes w/ DHF for DHFR enzyme

Identify the class

Purine Antagonists (Amidophosphoribosyl Transferase (APRT) Inhibitors)

Identify the class

Purine Antagonists (Amidophosphoribosyl Transferase (APRT) Inhibitors)

Identify the class

-DNA pol./ chain elongator inhibitor (gemcitabine here)

-note the altered ribose at the 2' position (DNA requires 2' Deoxy)

Identify the class, pharmacophore, and important moieties?

DNA polymerase/ chain elongator inhibitor (fluarabine phosphate here)

-note the 2'OH (DNA requires deoxy 2')

-note the halogen in the purine base

Identify the class, pharmacophore, and important moieties?

-DNA pol. / chain elongation inhibitor

-note the halogen in the base

-note this drug actually is 2' deoxy, unlike some others in this class

-MUST be triphosphorylated to intercalate into DNA and induce chain termination

Identify the class, pharmacophore, and important moieties?

oxetane

Identify the structure

Taxane -paclitaxel

Identify the class based on the structure

Taxane - docetaxel

Identify the class based on the structure

Vinca alkaloid - vincristine

Identify the class based on the structure

Note the different portions

-multicyclic portion on bottom is "vindoline portion"

-multicyclic portion on top is "catharanthine portion"

2-phenylaminopyrimidine

Identify the pharmacophore

4-anilinoquinazoline

Identify the pharmacophore

Tyrosine Kinase inhibitors

2-phenylaminopyrimidine and 4-anilinoquinazoline are seen in which anti-cancer class

TKIs and 2-phenylaminopyrimidine

Identify the class and pharmacophore

TKIs and 4-anilinoquinazoline

Identify the class and pharmacophore

bis-b-haloakylamine

Shown below are three nitrogen mustard (aziridine-activated) alkylating agents that are anticancer agents. Identify the pharmacophore that forms the reactive aziridine intermediate that cross-links DNA.

Shown below are 3 nitrosourea agents used to cross link DNA in the treatment of neoplasms. First, highlight the nitroso- group in each that is “unstable”. Secondly, highlight the nitrosourea pharmacophore of each. What “active” intermediate is formed that cross-links DNA? ANSWER SHOWN

Organoplatinum complexes

- Pt is key to cross-linking process

Identify the class. Which atom in the complex is the key to the cross-linking process?

Eventually metabolize to nitrogen gas and produces methyl cation (CH3)

Shown below are three DNA methylating agents employed to inactivate DNA in the treatment of cancer. What role do you think vicinal nitrogen atoms have in this process?

Highlighted is the likely methyl- groups that will methylate DNA molecules

Topoisomerase poisons

Identify the class

Shown below are 4 topoisomerase poisons Highlight the pentacycle (1) for each, and the lactone (2) in each.

purine

- non-nucleoside

- sulfur inhibits APRT reaction in purine synthesis

Shown below is a drug that is an antineoplastic agent. Identify if it is a pyrimidine vs. purine antagonists AND if it is a nucleoside.

Pyrimidine

- not a nucleoside

- fluorines inhibit thymidine synthase reaction.

Shown below is a drug that is an antineoplastic agent. Identify if it is a pyrimidine vs. purine antagonists AND if it is a nucleoside.

pyrimidine

- nucleoside

- note the methyl replacing the CH2-OH of normal nucleoside sugar-cant be phosphorylated

Shown below is a drug that is an antineoplastic agent. Identify if it is a pyrimidine vs. purine antagonists AND if it is a nucleoside.

pyrimidine

- nucleoside

- fluorines inhibit thymidine synthase reaction.

Shown below is a drug that is an antineoplastic agent. Identify if it is a pyrimidine vs. purine antagonists AND if it is a nucleoside.

Purine

- not a nucleoside

- sulfur inhibits APRT reaction in purine synthesis

Shown below is a drug that is an antineoplastic agent. Identify if it is a pyrimidine vs. purine antagonists AND if it is a nucleoside.

thymidine

Pyrimidine antagonists inhibit the production of which deoxynucleotide?

Purine: 3 and 4

Pyrimidine: 1 and 2

Nucleoside: 1,2, and 4

Nucleotide: 3

Shown below are 4 drugs that are DNA chain elongation inhibitors working as antineoplastic agents. Which are purine vs. pyrimidine agents? Are all of these nucleosides? Are any nucleotides?

taxane

The oxetane structure indicates it is a _________ agent

Taxanes: 1 and 3

Vinca Alkaloids: 2 and 4

Shown below are 4 drugs that serve as mitosis inhibitors in cancer chemotherapy. Which are taxanes and which are vinca alkaloids?

2-phenylaminopyrimidine

Shown is a tyrosine kinase inhibiting drug that is used as an antineoplastic. Identify whether it is a 2-phenylaminopyrimidine or 4-anilinoquinazoline pharmacophore

4-anilinoquinazoline

Shown is a tyrosine kinase inhibiting drug that is used as an antineoplastic. Identify whether it is a 2-phenylaminopyrimidine or 4-anilinoquinazoline pharmacophore

2-phenylaminopyrimidine

Shown is a tyrosine kinase inhibiting drug that is used as an antineoplastic. Identify whether it is a 2-phenylaminopyrimidine or 4-anilinoquinazoline pharmacophore

4-anilinoquinazoline

Shown is a tyrosine kinase inhibiting drug that is used as an antineoplastic. Identify whether it is a 2-phenylaminopyrimidine or 4-anilinoquinazoline pharmacophore

B and D

Which are NOT DNA-cross-linking agents? (select all that apply)

A, C, and D

Which are DNA methylating agents? (select all that apply

D

Which one of the following is not a topoisomerase poison?

A, C, E

Which are taxane mitosis inhibitors? (select all that apply)

B and C

Which highlighted components comprise the 2-phenylaminopyrimidine backbone of imatinib? (select all that apply)

D

Which is NOT a DNA cross linking agent?

B. chlorine

What component of chlorambucil is the leaving group to form the active Aziridinium ion

A. para-substituted aniline

B. chlorine

C. ethylchloride

D. carboxyl group

D. both the nitroso moiety and the urea component

Which molecular regions of carmustine represent components of the pharmacophore

A. both chlorines

B. only the central carbonyl

C. only the nitroso moiety

D. both the nitroso moiety and the urea component

A

Which is not a DNA methylator?

D. it has a pentacyclic lactone pharmacophore

Which is one true statement concerning irinotecan?

A. it is active as shown

B. it is an antineoplastic antibiotic

C. it has a quinolone pharmacophore

D. it has a pentacyclic lactone pharmacophore

3

Which one is the antineoplastic antibiotic

D

Which lettered ring in Epirubicin is NOT part of the 9,10-anthraquinone pharmacophore?

D

Which one of the antineoplastic agents does not have a lactone?

C

Which of these agents is ACTIVE as shown?

C (high blood levels with probable toxicity)

Therapeutic outcome in a LOW TPMT metabolizer treated with typical doses of azathioprine?

A. TPMT only effects pyrimidine drugs

B. therapeutically ineffective blood levels

C. high blood levels with probable toxicity

D. no effect

A. it is a nucleoside

which is the one true statement concerning clofarabine?

A. it is a nucleoside

B. it possesses a 3' fluorine

C. it contains a pyrimidine base

D. it is a nucleotide

3

Which region of paclitaxel is responsible for its description as a taxane mitosis inhibitor?

B. imatinib possesses a 2-phenylaminopyrimidine pharmacophore

Which is the one true statement about these tyrosine kinase inhibitors?

A. Both possess 2-phenylaminopyrimidine pharmacophore

B. imatinib possesses a 2-phenylaminopyrimidine pharmacophore

C. Erlotinib possesses a 2-phenylaminopyrimidine pharmacophore

D. both possess 4-anilinoquinazoline pharmacophores

2

Which one of these is not a mitosis inhibitor?

3

Which antineoplastic antibiotic is not a DNA intercalator?

B, D, and F

Which are NOT topoisomerase posions?

1, 4, and 5

Which circled oxygens are not part of the 9,10-anthraquinone pharmacophore?

A and C

Which are the bis-betahaloalkylamines?

B and D

Which of these agents are NOT taxane mitosis inhibitors?

2

Which circled oxygen is within the lactone component of the irinotecan pharmacophore?

4

Which highlighted nitrogen is not in the pharmacophore of imatinib

A, C, and E

Which of these agents will lead to cross linking of DNA

B

Which agent represents a DNA methylator?

B and D

Which compounds contain a 4-anilinoquinazoline pharmacophore

A, C, and D

Which agents are DNA methylators?

1

Which highlighted nitrogen is NOT part of the 4-anilinoquinazoline pharmacophore?

D and F

Which are the DNA methylator and the DNA cross linker?