Med Chem Final

Front 1

common precursor to cholesterol and ergosterol

Back 1

Squalene Epoxide

Front 2

Chitin

Back 2

structural carbohydrate formed by the enzyme, chitin synthase, and broken down by chitinase

Front 3

1, 3-beta-D-glucan synthesis inhibition

Back 3

inhibits cell wall biosynthesis makes cell walls weaker

Front 4

14-alpha-Lanosterol demethylase (CYP51A1)

Back 4

converts lanosterol to a precursor of ergosterol (not cholesterol)

Front 5

Agents that treat superficial dematophytoses (fungal infections) OTC

Back 5

1) Fatty acids = longish chain of fatty acids that decrease pH in fungal cells
2) Salicylic acid = decrease pH in fungal cell
3) Tolnaftate & allyl amines = distortion of hyphae
4) Ciclopirox = involves chelation & ion transport

Front 6

MOA of Griseofulvin

Back 6

binds dimers of alpha and beta tubulin to inhibit microtubule formation

Treats Deep dematophytoses (infections of skin and nails)

Front 7

MOA of Azole antifungals

Back 7

inhibition of CYP51 (15-alpha-lanosterol demethylase in fungi

Front 8

MOA of flucytosine

Back 8

PRODRUG

converted to 5-FU by fungi only ---inhibits fungal nucleotide synthesis

not toxic to humans

Front 9

MOA of polyene macrolides (amphotericin B, Nystatin, etc)

Back 9

association with ergosterol of fungal cell membrane to form pores, through which Potassium ions and other cell contents are lost = cells burst

Front 10

Side effects of polyene macrolides (amphotericin B & Nystatin)

Back 10

Nephrotoxicity = old formulations released drug to rapidly, distribution to kidneys too fast

Front 11

MOA of 1,3-beta-D-glucan synthesis inhibitors

Back 11

inhibit 1, 3 beta-D-glucan synthesis ==weak cell walls in fungi

Front 12

Viral Life Cycle

Back 12

1) Adsorption
2) Penetration
3) Uncoating
4) Early transcription
5) Early translation
6) DNA synthesis and late transcription
7) Late translation
8) condensation
9) assembly
10) Release

Front 13

HIV Cycle

Back 13

1) Virus attach and fusion
2) Reverse transcription
3) Integration
4) Transcription
5) Translation
6) Assemble, budding, maturation

Front 14

Targets of Antiviral Drug action

Back 14

1) inhibit viral attachment, penetration, and/or uncoating
2) Inhibit viral enzymes (nucleic acid biosynthesis)
3) Inhibit transcription of viral genome and translation of viral proteins
4) inhibit viral proteins
5) Interfere with post transcriptional modification of viral proteins
6) Interfere with viral componenet assembly
7) interfere with viral release

Front 15

MOA of Ionizable adamantane amine derivatives

Back 15

*Inhibit uncoating*

M2 protein in Flu Type A produce a proton transport channel

drug can plug proton transport channel, blocking transport of ions. Disturbs the pH balance AND prevents conformational change - no uncoating

Front 16

Ionizable Adamantane Amine Derivatives

Back 16

1) Amantadine (Symmetrel)
2) Rimantadine (Flumadine)

Front 17

Mechanism of Resistance to Ionizable Adamantane Amine Derivatives

Back 17

mutations in the transmembrane region of the M2 protein alter drug binding

Front 18

MOA of docosanol (Abreva)

Back 18

inhibit viral fusion

unusual phospholipids are incorporated into the cell membrane, diminishing the extent of viral fusion

Front 19

MOA of sialic acid analogs (Zanamavir, Oseltamavir)

Back 19

Neuraminidase catalyzes hydrolytic removal of sialic acid residue on host cell surface = link is broken, virion detach, infect another host cell

INHIBIT NEURAMINIDASE = decrease release of viral particles

Front 20

Resistance to sialic acid analogs (Zanamavir, Oseltamavir)

Back 20

site mutations of neuraminidase and hemagglutinin

Decrease binding affinity

Front 21

MOA of viral DNA strand elongation inhibitors (DNA Polymerase inhibitors)

Back 21

mimic dGTP and are incorporated by DNA polymerase into growing primer strand of DNA = terminate DNA chain elongation

competitive inhibitor of viral DNA polymerases, template unable to progress toward 5' end

Front 22

Bioactivation of DNA Polymerase inhibitors

Back 22

Pre-Prodrug (Viral Thymidine Kinase) Monophosphate (Host GMK) Tryphosphate

Front 23

Resistance to DNA Polymerase Inhibitors

Back 23

Mutations result in altered viral thymidine kinase or viral DNA polymerases

Front 24

MOA of Trifluorothymidine (DNA polymerase inhibitors)

Back 24

compete with dTTP for incorporation into a growing primer strand of DNA

Strand Elongation continues BUT modified base is unstable, falls off, and misreading of the DNA strand

Front 25

Resistance to Trifluorothymidine

Back 25

reduced viral thymidine kinase activity

Front 26

MOA of Foscarnet (DNA Polymerase Inhibition)

Back 26

competes with pyrophosphate for the pryophosphate binding site on DNA polymerase

prevents hydrolysis from dNTPs during chain elongation
**Also inhibits reverse transcriptase

Front 27

Resistance to Foscarnet

Back 27

mediated by alteration of viral DNA polymerase

Front 28

MOA of Ribavirin

Back 28

*Requires bioactivation*

RMP - inhibits inosine monophosphate dehydrogenase = decreased purine synthesis
RTP - inhibits viral RNA polymerases

Front 29

Resistance to Ribavirin

Back 29

mutation in viral RNA polymerases (drug can't bind)

Front 30

Targets for activity against HIV

Back 30

1) Attachment, fusion, uncoating
2) Reverse transcriptase
3) Integration, transcription, translation
4) HIV Protease

Front 31

MOA of Nucleoside-type Reverse Transcriptase Inhibitors (NRTIs)

Back 31

terminators of DNA strand elongation (No 3' - OH)

Front 32

Resistance of NRTIs

Back 32

point mutation in reverse transcriptase

Front 33

MOA of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Back 33

inactivates RT by a non-competitive mechanism via an allosteric binding site on the enzyme

do not interfere with normal binding of the substrate, SLOW DOWN the incorporation of dNTPs into the growing DNA strand

Front 34

Resistance of NNRTIs

Back 34

point mutations in reverse transcriptase = decreased binding at allosteric sites

Front 35

MOA of Protease Inhibitors (PI)

Back 35

inhibit the normal hydrolysis of hte bond between Tyr & Pro by a competitive mechanism

Gag-pol protein remains unprocessed - functional polypeptides not able to carry out their functions = viral progeny cannot infect new host cells

Front 36

Viral Fusion Inhibitors

Back 36

Drug Inhibits THIS:

1) Viral gp120 binds to host CD4 receptor = conformation change
2) binding site for CCR5 revealed = virus binds and another conformation change occurs
3) N-terminal hydrophobic region of gp41 exposed to CD4 receptor
4) heptad repeats of gp41 interact with one another = form hairpin structure = fuses viral/host cells

Front 37

MOA of Enfuvirtide

Back 37

*synthetic 36-residue peptide*

prevents interaction of HR1 & HR2 and the formation of the hairpin structure

Overall: NO HAIRPIN STRUCTURE = no viral fusion

Front 38

MOA of Maraviroc

Back 38

*CCR5 Receptor Antagonist*

blocks CCR5 and renders virus unable to fuse with and enter the host cell

Front 39

MOA of Integrase Inhibition

Back 39

inhibits the splicing of host genome and inserts viral double strand genome