ArticleAntimicrobial agents and chemotherapy2015
SQ109, a new drug lead for Chagas disease.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 81 citations in OpenAlex.
- Ιdentification of SQ109 analogs with enhanced antimicrobial activity against methicillin-resistantAntimicrobial agents and chemotherapy · 2026Article
- Adamantane-thiazole hybrids and related derivatives: synthesis, crystal structures, in vitro antibacterial, antifungal, and anti-proliferative activities.BMC chemistry · 2026Article
- Mechanistic Exploration ofPharmaceuticals (Basel, Switzerland) · 2026Article
- In vitro and in vivo efficacy of the antimycobacterial molecule SQ109 against the human pathogenic fungus, Cryptococcus neoformans.PLoS neglected tropical diseases · 2025Article
- Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Broad-Spectrum Activity and Mechanisms of Action of SQ109 on a Variety of Fungi.ACS infectious diseases · 2025Article
- The Tuberculosis Drug Candidate SQ109 and Its Analogs Have Multistage Activity againstACS infectious diseases · 2024Article
- Investigation into the Mechanism of Action of the Tuberculosis Drug Candidate SQ109 and Its Metabolites and Analogues in Mycobacteria.Journal of medicinal chemistry · 2023Article
- Synthesis and Testing of Analogs of the Tuberculosis Drug Candidate SQ109 against Bacteria and Protozoa: Identification of Lead Compounds againstACS infectious diseases · 2023Article
- The 1, 2-ethylenediamine SQ109 protects against tuberculosis by promoting M1 macrophage polarization through the p38 MAPK pathway.Communications biology · 2022Article
- Temporal and Wash-Out Studies Identify Medicines for Malaria Venture Pathogen Box Compounds with Fast-Acting Activity against BothMicroorganisms · 2022Article
- In Vivo Efficacy of SQ109 againstBiomedicines · 2022Article
- Advances in Key Drug Target Identification and New Drug Development for Tuberculosis.BioMed research international · 2022Review
- New possibilities for chromoblastomycosis and phaeohyphomycosis treatment: identification of two compounds from the MMV Pathogen Box® that present synergism with itraconazole.Memorias do Instituto Oswaldo Cruz · 2022Article
- The multi-target aspect of an MmpL3 inhibitor: The BM212 series of compounds bind EthR2, a transcriptional regulator of ethionamide activation.Cell surface (Amsterdam, Netherlands) · 2021Article
- Structure,ACS infectious diseases · 2021Article
- Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box.Nature communications · 2021Article
- Hydroxylation of Antitubercular Drug Candidate, SQ109, by Mycobacterial Cytochrome P450.International journal of molecular sciences · 2020Article
- SAR Analysis of Small Molecules Interfering with Energy-Metabolism inPharmaceuticals (Basel, Switzerland) · 2020Review
- Antibiotics in the clinical pipeline in October 2019.The Journal of antibiotics · 2020Review
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 5 countries.
Funding
Abstract
We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, may also have potential as a drug lead 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.