ArticlePLoS pathogens2014
Squalene synthase as a target for Chagas disease therapeutics.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 73 citations in OpenAlex.
- Candimine as a natural scaffold for targeting squalene synthetase in Trypanosoma cruzi: insights from computational studies.Molecular diversity · 2026Article
- Exploring the Anti-Chagas Activity ofPlants (Basel, Switzerland) · 2025Article
- Innovations in Antifungal Drug Discovery among Cell Envelope Synthesis Enzymes through Structural Insights.Journal of fungi (Basel, Switzerland) · 2024Review
- Anti-Molecules (Basel, Switzerland) · 2023Article
- Review
- Article
- A Structural and Bioinformatics Investigation of a Fungal Squalene Synthase and Comparisons with Other Membrane Proteins.ACS omega · 2022Article
- Benzylamines as highly potent inhibitors of the sterol biosynthesis pathway in Leishmania amazonensis leading to oxidative stress and ultrastructural alterations.Scientific reports · 2022Article
- Article
- The translational challenge in Chagas disease drug development.Memorias do Instituto Oswaldo Cruz · 2022Review
- Metabolic flexibility in Trypanosoma cruzi amastigotes: implications for persistence and drug sensitivity.Current opinion in microbiology · 2021Review
- Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase fromHeliyon · 2021Article
- An Overview on the Therapeutics of Neglected Infectious Diseases-Leishmaniasis and Chagas Diseases.Frontiers in chemistry · 2021Review
- Nano-Medicines a Hope for Chagas Disease!Frontiers in molecular biosciences · 2021Review
- Structure, catalysis, and inhibition mechanism of prenyltransferase.IUBMB life · 2021Review
- Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning.International journal of molecular sciences · 2020Article
- Three Alkaloids from an Apocynaceae Species,Plants (Basel, Switzerland) · 2020Article
- Nanotechnological interventions for treatment of trypanosomiasis in humans and animals.Drug delivery and translational research · 2020Article
- High-Throughput Screening of the ReFRAME Library Identifies Potential Drug Repurposing Candidates forMicroorganisms · 2020Article
- Transcriptome analysis of Clinopodium gracile (Benth.) Matsum and identification of genes related to Triterpenoid Saponin biosynthesis.BMC genomics · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 10 institutions in 6 countries.
Funding
Abstract
Trypanosomatid parasites are the causative agents of many neglected tropical diseases and there is currently considerable interest in targeting endogenous sterol biosynthesis in these organisms as a route to the development of novel anti-infective drugs. Here, we report the first x-ray crystallographic structures of the enzyme squalene synthase (SQS) from a trypanosomatid parasite, Trypanosoma cruzi, the causative agent of Chagas disease. We obtained five structures of T. cruzi SQS and eight structures of human SQS with four classes of inhibitors: the substrate-analog S-thiolo-farnesyl diphosphate, the quinuclidines E5700 and ER119884, several lipophilic bisphosphonates, and the thiocyanate WC-9, with the structures of the two very potent quinuclidines suggesting strategies for selective inhibitor development. We also show that the lipophilic bisphosphonates have low nM activity against T. cruzi and inhibit endogenous sterol biosynthesis and that E5700 acts synergistically with the azole drug, posaconazole. The determination of the structures of trypanosomatid and human SQS enzymes with a diverse set of inhibitors active in cells provides insights into SQS inhibition, of interest in the context of the development of drugs against Chagas disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.