Malaria Egress Pathway and UA2239 Inhibition
24 Questions
2 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the ED50 of UA2239 in inhibiting berghei-infected mice?

  • 0.1 mg/kg
  • 0.5 mg/kg (correct)
  • 1.0 mg/kg
  • 2.0 mg/kg

What does a high selectivity index (SI > 10,000) for UA2239 indicate?

  • Broad-spectrum antiviral properties
  • Low toxicity to mammalian cells (correct)
  • High activity on mammalian cells
  • Enhanced side effects

Which pathway is involved in the egress of merozoites from red blood cells?

  • cGMP-PDE pathway
  • Calcium-dependent pathway
  • cGMP-PKG dependent pathway (correct)
  • cAMP-PKA pathway

What is the expected effect of inhibiting PfPDE?

<p>Induced egress of immature merozoites (A)</p> Signup and view all the answers

Which chemical class does Compound 2 (C2) belong to?

<p>Imidazopyridines (B)</p> Signup and view all the answers

How does UA2239 affect different stages of the parasite life cycle?

<p>Inhibits both intraerythrocytic cycle and gametogenesis (A)</p> Signup and view all the answers

The primary mechanism of action for nucleoside and nucleotide analogues involves what process?

<p>Conversion into poly-phosphorylated derivatives (A)</p> Signup and view all the answers

What is the result of inhibiting PfPKG in malaria parasites?

<p>Impairment of merozoite egress from red blood cells (A)</p> Signup and view all the answers

What is the target of the compound UA2239 in the malaria parasite?

<p>Guanylate cyclase (PfGCα) (B)</p> Signup and view all the answers

What distinguishes UA2239's mechanism of action from traditional antimalarial therapies?

<p>It impairs cyclic-GMP synthesis. (D)</p> Signup and view all the answers

In which aspect has UA2239 shown significant promise?

<p>Inhibiting the growth of Plasmodium in vitro and in animal models. (C)</p> Signup and view all the answers

What does UA2239 inhibit in the malaria lifecycle?

<p>Egress of merozoites and gametes from erythrocytes. (C)</p> Signup and view all the answers

What phenomenon was observed with UA2239-resistant P.falciparum lines?

<p>Mutations in cGMP-dependent protein kinase (PKG). (A)</p> Signup and view all the answers

How many deaths due to malaria were estimated in 2022?

<p>608,000 (D)</p> Signup and view all the answers

What role does guanylate cyclase (PfGCα) play in the context of UA2239's action?

<p>It is inhibited by UA2239. (B)</p> Signup and view all the answers

What is the main urgent need mentioned for antimalarial therapies?

<p>To combat the spread of malaria parasite resistance. (C)</p> Signup and view all the answers

What remains a critical method in the fight against malaria despite the development of vaccines?

<p>Chemotherapy (B)</p> Signup and view all the answers

Which of the following accurately describes the life cycle of the malaria parasite in humans?

<p>They initially multiply in liver cells before entering the bloodstream. (C)</p> Signup and view all the answers

What is a significant issue faced in malaria treatment currently?

<p>Emergence of artemisinin-resistant strains (B)</p> Signup and view all the answers

What is the expected focus of future antimalarial treatments?

<p>Targeting multiple stages of the parasite's life cycle (B)</p> Signup and view all the answers

Which of the following statements describes the activity of the compound UA2239?

<p>It inhibits parasite growth effectively in vitro. (C)</p> Signup and view all the answers

What does the IC50 value indicate in the context of UA2239's effectiveness?

<p>The concentration required to inhibit 50% of parasite growth. (A)</p> Signup and view all the answers

What is the role of gametocytes in the malaria parasite's life cycle?

<p>To mate in the mosquito gut after a blood meal. (C)</p> Signup and view all the answers

What has recently been synthesized as a novel antimalarial treatment?

<p>Acyclo-nucleoside phosphonates (ANPs) (A)</p> Signup and view all the answers

Flashcards

Antimalarial therapy

A treatment for malaria, typically targeting Plasmodium parasites.

UA2239

An acyclic nucleoside phosphonate and purine analog, exhibiting robust malaria parasite growth inhibition.

cGMP-dependent protein kinase (PKG)

An enzyme essential for malaria parasite egress from red blood cells.

Resistance phenotype

A specific trait that appears in parasites due to mutations in genes, making them resistant to a drug (UA2239).

Signup and view all the flashcards

Guanylate cyclase (PfGCα)

Likely primary target of UA2239; responsible for cGMP generation.

Signup and view all the flashcards

Egress pathway

The process of malaria parasite exit from red blood cells.

Signup and view all the flashcards

Malaria parasite resistance

The ability of malaria parasites to withstand the actions of drugs currently used against infection.

Signup and view all the flashcards

Cyclic GMP

A crucial molecule in the malaria parasite egress process.

Signup and view all the flashcards

Malaria Cases

Malaria cases and deaths have been decreasing slowly but are still higher than before the COVID-19 pandemic.

Signup and view all the flashcards

Malaria Vaccines

Early malaria vaccines are being used in some African countries, while many vaccine candidates are in development.

Signup and view all the flashcards

Artemisinin-resistance

Parasites resistant to artemisinin, a crucial treatment for malaria, are emerging in Asia and Africa.

Signup and view all the flashcards

Chemotherapy in Malaria

Chemotherapy is still essential for malaria treatment, especially with the current use of artemisinin combination therapy

Signup and view all the flashcards

New Antimalarial Treatments

Future malaria treatments will target multiple stages of the parasite's life cycle in both humans and mosquitoes.

Signup and view all the flashcards

Parasite Life Cycle (human)

Malaria parasites initially multiply in liver cells, then grow and multiply in red blood cells (invasion-growth-multiplication).

Signup and view all the flashcards

Parasite Life Cycle (mosquito)

A fraction of parasites become gametocytes, which mature and mate in the mosquito gut, before settling in the salivary glands for transmission.

Signup and view all the flashcards

ED50 of UA2239

Effective dose of UA2239 to inhibit 50% parasite growth (intraperitoneal administration)

Signup and view all the flashcards

Selectivity Index (SI) of UA2239

Ratio of doses needed to affect mammalian cells versus parasite cells (SI > 10,000 for UA2239).

Signup and view all the flashcards

Mechanism of Nucleoside/Nucleotide Analogues

Converted to poly-phosphorylated derivatives and interact with cellular or viral polymerases (substrate or inhibitor).

Signup and view all the flashcards

ANPs inhibiting Plasmodium enzymes

Anti-malarial drugs target the purine salvage pathway in Plasmodium.

Signup and view all the flashcards

UA2239's effect on merozoite egress

Disrupts merozoite egress, a process governed by cGMP-PKG dependent pathway, rather than DNA synthesis.

Signup and view all the flashcards

cGMP-PKG pathway

Governs merozoite egress; activation of protein kinase G (PKG) requires cGMP.

Signup and view all the flashcards

PfPKG inhibitor effect

Impairs merozoite egress, blocking parasites in red blood cells, similar inhibitory effect with PfGC inhibition

Signup and view all the flashcards

PfPDE inhibition effect

Stimulates premature egress of immature merozoites, rendering them unable to infect new red blood cells.

Signup and view all the flashcards

Study Notes

Malaria cGMP-PKG Dependent Egress Pathway Inhibited by UA2239

  • A potent acyclic nucleoside phosphonate, UA2239, inhibits the malaria cGMP-PKG dependent egress pathway.
  • UA2239 inhibits Plasmodium growth in vitro and in animal models.
  • It blocks the egress of merozoites and gametes from erythrocytes.
  • UA2239 resistance in P. falciparum is linked to mutations in cGMP-dependent protein kinase (PKG).
  • However, UA2239 doesn't directly target PKG; instead, it lowers cGMP levels.
  • This, in turn, inhibits the parasite's guanylate cyclase (PfGCa), which is a crucial component of the cGMP-dependent egress pathway.
  • UA2239 impairs cyclic-GMP synthesis.
  • This uniquely targets the unique mechanism of action by targeting cyclic GMP synthesis.

Abbreviations

  • C2: compound 2
  • CQ: chloroquine
  • DHA: dihydroartemisinin
  • GC: guanylate cyclase
  • GER parasites: genome-edited resistant parasites

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

UA2239 Inhibits Malaria cGMP-PKG Pathway PDF

Description

This quiz explores the role of UA2239 in inhibiting the malaria cGMP-PKG dependent egress pathway. Test your understanding of its effects on Plasmodium growth, mutation links, and its unique mechanism of action targeting cyclic GMP synthesis.

More Like This

Malaria Quiz
9 questions

Malaria Quiz

SucceedingChrysoprase avatar
SucceedingChrysoprase
Malaria Overview and Life Cycle
12 questions

Malaria Overview and Life Cycle

ReputableTangent4657 avatar
ReputableTangent4657
Malaria PKG Structure and Activation
24 questions

Malaria PKG Structure and Activation

HottestSense2831 avatar
HottestSense2831
Use Quizgecko on...
Browser
Open
Browser
Browser