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Anthelminthic Agents01:15

Anthelminthic Agents

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Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
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Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
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Targeting Kinetoplastid Parasites with ProTide Prodrugs: A Proof-of-Concept Study.

Silvester Lowe1, Vishal Satikuvar1, Tanjia M Syeda1

  • 1Department of Pharmacy, School of Life Sciences, Pharmacy and Chemistry, Kingston University, London, UK.

Chemmedchem
|April 3, 2026
PubMed
Summary

ProTide prodrug technology enhances nucleoside analogues for treating neglected tropical diseases. A novel compound showed potent activity against kinetoplastid parasites, offering a promising new therapeutic strategy.

Keywords:
cordycepinkinetoplastidsneglected tropical diseasesnucleoside analoguesproTide

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Area of Science:

  • Medicinal Chemistry
  • Parasitology
  • Drug Discovery

Background:

  • Neglected tropical diseases (NTDs) pose significant global health challenges, disproportionately affecting low- and middle-income countries.
  • Kinetoplastid parasites (causing Chagas disease, leishmaniasis, African trypanosomiasis) depend on host purine salvage pathways, making nucleoside analogues potential drug candidates.
  • Existing nucleoside analogues face limitations due to poor cellular uptake and rapid metabolism, hindering their clinical application.

Purpose of the Study:

  • To apply the clinically validated ProTide prodrug technology for improved intracellular delivery of nucleoside analogues against kinetoplastid parasites.
  • To design, synthesize, and evaluate a library of zidovudine (AZT) and cordycepin ProTide prodrugs for antiparasitic activity and cytotoxicity.

Main Methods:

  • Synthesis of a focused library of AZT and cordycepin ProTide prodrugs.
  • Evaluation of antiparasitic activity against Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani.
  • Assessment of cytotoxicity using L6 rat myoblasts.

Main Results:

  • Compound 16 demonstrated significant serum stability.
  • Compound 16 exhibited potent activity against T. b. rhodesiense (IC50 = 5 nM; SI = 2,560).
  • Compound 16 also showed robust activity against T. cruzi and L. donovani.

Conclusions:

  • The ProTide prodrug technology is a viable strategy for optimizing nucleoside analogues for treating kinetoplastid infections.
  • This approach provides a framework for developing novel therapeutics against neglected tropical diseases.
  • Compound 16 represents a promising lead candidate for further development.