Evidence map›Paper›PMID 29740005›Full record

ArticleScientific reports2018

Nitrothiophene carboxamides, a novel narrow spectrum antibacterial series: Mechanism of action and Efficacy.

Shahul Hameed P, Nagakumar Bharatham, Nainesh Katagihallimath, Sreevalli Sharma, Radha Nandishaiah, Anirudh P Shanbhag, Teby Thomas, Riya Narjari, Maitrayee Sarma, Purnendu Bhowmik and 8 more

Abstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Shahul Hameed PBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Nagakumar BharathamCentre for Cellular and Molecular Platforms (C-CAMP), National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Nainesh KatagihallimathBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Sreevalli SharmaBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Radha NandishaiahBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Anirudh P ShanbhagBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Teby ThomasSt. John's Research Institute, 100 Feet Rd, John Nagar, Koramangala, Bengaluru, Karnataka, 560034, India.
Riya NarjariBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Maitrayee SarmaBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Purnendu BhowmikBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Prakruthi AmarBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Rajani RavishankarBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Ramesh JayaramanTheraIndx Lifesciences Pvt. Ltd., Sy No. 27, Deganahalli, Budihal Post, Nelamangala, Karnataka, 562123, India.
Kubendran MuthanSyngene International Ltd., Plot 2 & 3, Bommasandra Industrial Estate - Phase-IV, Bommasandra-Jigani Link Road, Bengaluru, Karnataka, 560099, India.
Ramesh SubbiahSyngene International Ltd., Plot 2 & 3, Bommasandra Industrial Estate - Phase-IV, Bommasandra-Jigani Link Road, Bengaluru, Karnataka, 560099, India.
Vasanthi RamachandranBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
V BalasubramanianBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India.
Santanu DattaBUGWORKS Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, GKVK, Bellary Rd, Bengaluru, Karnataka, 560065, India. santanu@bugworksresearch.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The mechanism of efflux is a tour-de-force in the bacterial armoury that has thwarted the development of novel antibiotics. We report the discovery of a novel chemical series with potent antibacterial properties that was engineered to overcome efflux liability. Compounds liable to efflux specifically via the Resistance Nodulation and cell Division (RND) pump, AcrAB-TolC were chosen for a hit to lead progression. Using structure-based design, the compounds were optimised to lose their binding to the efflux pump, thereby making them potent on wild-type bacteria. We discovered these compounds to be pro-drugs that require activation in E. coli by specific bacterial nitroreductases NfsA and NfsB. Hit to lead chemistry led to the generation of compounds that were potent on wild-type and multi-drug resistant clinical isolates of E. coli, Shigella spp., and Salmonella spp. These compounds are bactericidal and efficacious in a mouse thigh infection model.

Indexed as

AnimalsAnti-Bacterial AgentsCell DivisionDrug Resistance, Multiple, BacterialEscherichia coli ProteinsHumansMiceMicrobial Sensitivity TestsProdrugsProtein ConformationSalmonellaShigellaThiophenesAnti-Bacterial AgentsEscherichia coli ProteinsProdrugsThiophenes

Identifiers

PMID29740005
PMCPMC5940854

What OpenQuestion holds

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Registered trials

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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.