Antineoplastic Agents Flashcards Preview

Med Chem > Antineoplastic Agents > Flashcards

Flashcards in Antineoplastic Agents Deck (27):
1

Neoplasm

Uncontrolled and abnormal growth of tissue in animals or plants (aka tumor)

2

Targets of cancer chemotherapy

Cellular processes that are prevalent in rapidly-dividing cells
Leads to onset of side effects (hair loss, immune deficiencies, nausea)

3

What cancer chemotherapeutics must do in order to prevent remission

Must be able to kill every cancer cell
Unfortunately, most antineoplastic agents kill cells by first order kinetics (never actually kill every single cell)

4

Tumor cell properties

Uncontrolled cell proliferation
Decreased cellular differentiation
Capacity to invade surrounding tissue
Ability to establish growth at remote sites (metastasis)

5

How tumor cells bypass apoptosis

Reduce or remove tumor suppressor proteins (ex-p53)

6

Intrinsic apoptosis mechanism

Cyctochrome c is released from the mitochondria

7

Extrinsic apoptosis mechanism

TNF-family interacts with "death receptors"

8

Alkylating agents

Most effective against fast-growing tumors
Alkylate nucleic acids

9

Guanine alkylation

N-7 atom of guanine is particularly nucleophilic and prone to reaction with alkylating agents
N-7-alkylated guanine is unstable and decomposes

10

Nitrogen mustards

Contain nitrogen atom and one or more beta-halogens
Nitrogen attacks alkyl halide carbon atom, forming an aziridinium atom, a strong electrophile
Example: chlorambucil

11

Cyclophosphamide

Prodrug version of nitrogen mustard

12

Platinum agents

Certain cis-platinum complexes have antitumor activity
Inhibit DNA polymerase by forming intrastrand bis-alkylated adducts
Examples: cisplatin, carboplatin

13

N-alkyl-N-nitrosoureas

Decompose to isocyanates and diazohydroxides
Example: carmustine

14

Mitomycin C

Requires metabolic reduction of its quinone to a hydroquinone
Double alkylating agent: can crosslink DNA

15

Antimetabolites

Inhibit the biosynthesis of normal cellular metabolites
Most target the biosynthesis of nucleic acids
Examples: 5-fluorouracil, 6-mercaptopurine

16

5-fluorouracil

Metabolite, 5-fluoro-deoxyuracil monophosphate (5-fluoro-dUMP), inhibits thymidylate synthase
Blocks conversion of dUMP to dTMP
Lacks the proton required for the normal uracil to thymine mechanism

17

Thiol-containing purines

Inhibit ability to form purine metabolites
Examples: 6-mercaptopurine, thioguanine

18

Vidarabine and fludarabine

Commonly called adenine arabinosides
Competitive inhibitors of DNA polymerase

19

Folic acid antimetabolites

Inhibit DNA synthesis by irreversibly binding to dihydrofolate reductase
Examples: aminopterin, methotrexate

20

Antineoplastic antibiotics

Microbial origin
Diverse methods of targeting DNA: intercalation, alkylation, strand breakage through formation of radicals

21

Dactinomycin

Antineoplastic antibiotic
2 cyclic peptides attached to a 3-ring system
Intercalates into double-stranded DNA and inhibits topoisomerase II

22

Anthracyclines

Glycosylated tetracyclic anthraquinone core
Intercalates double-stranded DNA and inhibits topoisomerase II
Reduction of quinone can lead to formation of hydroxyl radicals and DNA strand scission

23

Camptothecins

Inhibitors of topoisomerase I, which normally produces short-term, single-strand breaks in DNA to add/release supercoiling
Can also intercalate (many-ringed systems)

24

Bleomycins

Chelators of copper (blue color)
Form a chelate with Fe (II) that can bind molecular O2, leading to formation of hydroxyl and superoxide radicals

25

Vinca alkaloids

Alkaloids: nitrogen-containing heterocycles from plants
Examples: vincristine, vinblastine
Cause mitotic arrest by promoting dissolution of microtubules

26

Paclitaxel

World's top-selling antitumor drug (Taxol)
Inhibits mitosis by binding tubulin and preventing its depolymerization
Different tubulin binding site than vinca alkaloids

27

Mitomycins

3 features: quinone (redox activation), carbamate (electrophile), aziridine (electrophile)
Bisfunctional alkylating agents
Redox cycles can generate hydrogen peroxide near DNA