ArticlePLoS neglected tropical diseases2017
Structurally optimized analogs of the retrograde trafficking inhibitor Retro-2cycl limit Leishmania infections.
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Retrograde trafficking inhibitors allosterically trap Get3 to block tail-anchored protein biogenesis.bioRxiv : the preprint server for biology · 2026Article
- Labeling strategies to track protozoan parasite proteome dynamics.Current opinion in chemical biology · 2023Review
- Mechanisms and Minimization of False Discovery of Metabolic Bioorthogonal Noncanonical Amino Acid Proteomics.Rejuvenation research · 2022Article
- Thermoresponsive Copolymer Nanovectors Improve the Bioavailability of Retrograde Inhibitors in the Treatment ofFrontiers in cellular and infection microbiology · 2021Article
- The macrophage microtubule network acts as a key cellular controller of the intracellular fate of Leishmania infantum.PLoS neglected tropical diseases · 2020Article
- A quantitative single-cell assay for retrograde membrane traffic enables rapid detection of defects in cellular organization.Molecular biology of the cell · 2020Article
- DH82 Canine and RAW264.7 Murine Macrophage Cell Lines Display Distinct Activation Profiles Upon Interaction WithFrontiers in cellular and infection microbiology · 2020Article
- Discovery of Retro-1 Analogs Exhibiting Enhanced Anti-vaccinia Virus Activity.Frontiers in microbiology · 2020Article
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6 authors.
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Abstract
In infected mammalian cells, Leishmania parasites reside within specialized compartments called parasitophorous vacuoles (LPVs). We have previously shown that Retro-2, a member of a novel class of small retrograde pathway inhibitors caused reduced LPV sizes and lower parasite numbers during experimental L. mexicana sp. infections. The purpose of this study was to determine if structural analogs of Retro-2cycl reported to have superior potency in the inhibition of retrograde pathway-dependent phenomena (i.e., polyomavirus cellular infection by polyomavrius and Shiga toxin trafficking in cells) are also more effective than the parent compound at controlling Leishmania infections. In addition to their effects on LPV development, we show that two optimized analogs of Retro-2cycl, DHQZ 36 and DHQZ 36.1 limit Leishmania amazonensis infection in macrophages at EC50 of 13.63+/-2.58μM and10.57+/-2.66μM, respectively, which is significantly lower than 40.15μM the EC50 of Retro-2cycl. In addition, these analogs caused a reversal in Leishmania induced suppression of IL-6 release by infected cells after LPS activation. Moreover, we show that in contrast to Retro-2cycl that is Leishmania static, the analogs can kill Leishmania parasites in axenic cultures, which is a desirable attribute for any drug to treat Leishmania infections. Together, these studies validate and extend the published structure-activity relationship analyses of Retro-2cycl.
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