ArticleACS medicinal chemistry letters2015
Left-Hand Side Exploration of Novel Bacterial Topoisomerase Inhibitors to Improve Selectivity against hERG Binding.
Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 16 citations in OpenAlex.
- Structural Aspects ofACS medicinal chemistry letters · 2024Article
- Molecular mechanism of a triazole-containing inhibitor ofiScience · 2024Article
- Spiropyrimidinetrione DNA Gyrase Inhibitors with Potent and Selective Antituberculosis Activity.Journal of medicinal chemistry · 2022Article
- Structure-Activity Relationship of Anti-ACS medicinal chemistry letters · 2022Article
- Editorial: Medicinal Chemistry Research in India.ACS medicinal chemistry letters · 2017Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Structure-activity relationship (SAR) exploration on the left-hand side (LHS) of a novel class of bacterial topoisomerase inhibitors led to a significant improvement in the selectivity against hERG cardiac channel binding with concomitant potent antimycobacterial activity. Bulky polar substituents at the C-7 position of the naphthyridone ring did not disturb its positioning between two base pairs of DNA. Further optimization of the polar substituents on the LHS of the naphthyridone ring led to potent antimycobacterial activity (Mtb MIC = 0.06 μM) against Mycobacterium tuberculosis (Mtb). Additionally, this knowledge provided a robust SAR understanding to mitigate the hERG risk. This compound class inhibits Mtb DNA gyrase and retains its antimycobacterial activity against moxifloxacin-resistant strains of Mtb. Finally, we demonstrate in vivo proof of concept in an acute mouse model of TB following oral administration of compound 19.
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Registered trials
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