ArticleAntimicrobial agents and chemotherapy2007
Kinetic characterization of squalene synthase from Trypanosoma cruzi: selective inhibition by quinuclidine derivatives.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 58 citations in OpenAlex.
- A Novel Dual-Target Compound Designed With Potent Herbicidal and Fungicidal Activity Inspired by Conserved Phytoene Synthase Domains.Plant biotechnology journal · 2026Article
- Selenocyanate-Containing Molecules as Trypanosoma cruzi Inhibitors: Impact of Regioisomerism, Conformational Restriction, and Second-Ring Substitution.ChemMedChem · 2026Article
- Antimicrobial and Anesthetic Niosomal Formulations Based on Amino Acid-Derived Surfactants.Molecules (Basel, Switzerland) · 2024Article
- Review
- Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Pharmaceutics · 2023Article
- A Structural and Bioinformatics Investigation of a Fungal Squalene Synthase and Comparisons with Other Membrane Proteins.ACS omega · 2022Article
- Quantitative Structure-Activity Relationships for Structurally Diverse Chemotypes Having Anti-International journal of molecular sciences · 2019Article
- Activity of Fluorine-Containing Analogues of WC-9 and Structurally Related Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma gondii.ChemMedChem · 2016Article
- Directed optimization of a newly identified squalene synthase from Mortierella alpine based on sequence truncation and site-directed mutagenesis.Journal of industrial microbiology & biotechnology · 2015Article
- SQ109, a new drug lead for Chagas disease.Antimicrobial agents and chemotherapy · 2015Article
- Squalene synthase as a target for Chagas disease therapeutics.PLoS pathogens · 2014Article
- Genetic profiling of the isoprenoid and sterol biosynthesis pathway genes of Trypanosoma cruzi.PloS one · 2014Article
- Functional characterization and differential expression studies of squalene synthase from Withania somnifera.Molecular biology reports · 2012Article
- 2-alkylaminoethyl-1,1-bisphosphonic acids are potent inhibitors of the enzymatic activity of Trypanosoma cruzi squalene synthase.Antimicrobial agents and chemotherapy · 2012Article
- Head-to-head prenyl tranferases: anti-infective drug targets.Journal of medicinal chemistry · 2012Article
- Mechanism of action and inhibition of dehydrosqualene synthase.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Cloning and characterization of squalene synthase gene from Fusarium fujikuroi (Saw.) Wr.Journal of industrial microbiology & biotechnology · 2010Article
- Synthetic Medicinal Chemistry in Chagas' Disease: Compounds at The Final Stage of "Hit-To-Lead" Phase.Pharmaceuticals (Basel, Switzerland) · 2010Review
- New, improved treatments for Chagas disease: from the R&D pipeline to the patients.PLoS neglected tropical diseases · 2009Review
- Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs.Interdisciplinary perspectives on infectious diseases · 2009Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biosynthesis of sterols is a major route for the development of antitrypanosomals. Squalene synthase (SQS) catalyzes the first step committed to the biosynthesis of sterols within the isoprenoid pathway, and several inhibitors of the enzyme have selective antitrypanosomal activity both in vivo and in vitro. The enzyme from Trypanosoma cruzi is a 404-amino-acid protein with a clearly identifiable membrane-spanning region. In an effort to generate soluble recombinant enzyme, we have expressed in Escherichia coli several truncated versions of T. cruzi SQS with a His tag attached to the amino terminus. Deletions of both the amino- and carboxyl-terminal regions generated active and soluble forms of the enzyme. The highest levels of soluble protein were achieved when 24 and 36 amino acids were eliminated from the amino and carboxyl regions, respectively, yielding a protein of 41.67 kDa. The Michaelis-Menten constants of the purified enzyme for farnesyl diphosphate and NAD (NADPH) were 5.25 and 23.34 microM, respectively, whereas the V(max) was 1,428.56 nmol min(-1)mg(-1). Several quinuclidine derivatives with antiprotozoal activity in vitro were found to be selective inhibitors of recombinant T. cruzi SQS in comparative assays with the human enzyme, with 50% inhibitory concentration values in the nanomolar range. These data suggest that selective inhibition of T. cruzi SQS may be an efficient strategy for the development of new antitrypanosomal agents.
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