ArticleJournal of medicinal chemistry2018
Indolyl Azaspiroketal Mannich Bases Are Potent Antimycobacterial Agents with Selective Membrane Permeabilizing Effects and in Vivo Activity.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 34 citations in OpenAlex.
- A potent phenylalkylamine disrupts mycobacterial membrane bioenergetics and augments bactericidal activity of bedaquiline.iScience · 2025Article
- Spirocyclic compounds: potential drug leads in the fight againstFuture medicinal chemistry · 2025Review
- Mannich Bases: Promising Scaffolds for the Treatment of Infectious Diseases.Current medicinal chemistry · 2025Review
- In Vitro Resistance-Predicting Studies and In Vitro Resistance-Related Parameters-A Hit-to-Lead Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Alkyltriphenylphosphonium turns naphthoquinoneimidazoles into potent membrane depolarizers againstRSC medicinal chemistry · 2022Article
- A new strategy for hit generation: Novel in cellulo active inhibitors of CYP121A1 from Mycobacterium tuberculosis via a combined X-ray crystallographic and phenotypic screening approach (XP screen).European journal of medicinal chemistry · 2022Article
- Structural Rigidification ofACS medicinal chemistry letters · 2022Article
- Functionalized Dioxonaphthoimidazoliums: A Redox Cycling Chemotype with Potent Bactericidal Activities againstJournal of medicinal chemistry · 2021Article
- Resistance against Membrane-Inserting MmpL3 Inhibitor through Upregulation of MmpL5 in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2020Article
- Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020Review
- MmpL3 Inhibition: A New Approach to Treat Nontuberculous Mycobacterial Infections.International journal of molecular sciences · 2020Review
- Potency Increase of Spiroketal Analogs of Membrane Inserting Indolyl Mannich Base Antimycobacterials Is Due to Acquisition of MmpL3 Inhibition.ACS infectious diseases · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The inclusion of an azaspiroketal Mannich base in the membrane targeting antitubercular 6-methoxy-1- n-octyl-1 H-indole scaffold resulted in analogs with improved selectivity and submicromolar activity against Mycobacterium tuberculosis H37Rv. The potency enhancing properties of the spiro-fused ring motif was affirmed by SAR and validated in a mouse model of tuberculosis. As expected for membrane inserting agents, the indolyl azaspiroketal Mannich bases perturbed phospholipid vesicles, permeabilized bacterial cells, and induced the mycobacterial cell envelope stress reporter promoter p iniBAC. Surprisingly, their membrane disruptive effects did not appear to be associated with bacterial membrane depolarization. This profile was not uniquely associated with azaspiroketal Mannich bases but was characteristic of indolyl Mannich bases as a class. Whereas resistant mycobacteria could not be isolated for a less potent indolyl Mannich base, the more potent azaspiroketal analog displayed low spontaneous resistance mutation frequency of 10
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Registered trials
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.