Drug resistance reversal potential of multifunctional thieno[3,2-c]pyran via potentiation of antibiotics in MDR P. aeruginosa

Background: Due to the limited availability of antibiotics, Gram-negative bacteria (GNB) acquire different levels of drug resistance. It raised an urgent need to identify such agents, which can reverse the phenomenon of drug resistance. Objective: To understand the mechanism of drug resistance reversal of glycosides; niaziridin and niazirin isolated from the pods of Moringa oleifera and ouabain (control) against the clinical isolates of multidrug-resistant Escherichia coli. Methods: The MICs were determined following the CLSI guidelines for broth micro-dilution. In-vitro combination studies were performed by broth checkerboard method followed by Time-Kill studies, the efflux pump inhibition assay, ATPase inhibitory activity, mutation prevention concentration and in-silico studies. Results: The results showed that both glycosides did not possess antibacterial activity of their own, but in combination, they reduced the MIC of tetracycline up to 16 folds. Both were found to inhibit efflux pumps, but niaziridin was the best. In real time expression pattern analysis, niaziridin was also found responsible for the down expression of the two important efflux pump acrB & yojI genes alone as well as in combination. Niaziridin was also able to over express the porin forming genes (ompA & ompX). These glycosides decreased the mutation prevention concentration of tetracycline. Conclusion: This is the first ever report on glycosides, niazirin and niaziridin acting as drug resistance reversal agent through efflux pump inhibition and modulation of expression pattern drug resistant genes. This study may be helpful in preparing an effective antibacterial combination against the drug-resistant GNB from a widely growing Moringa oleifera.

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Drug Resistance Reversal Potential of Ursolic Acid Derivatives against Nalidixic Acid- and Multidrug-resistantEscherichia coli

Chemical Biology & Drug Design ◽

10.1111/cbdd.12491 ◽

2015 ◽

Vol 86 (3) ◽

pp. 272-283 ◽

Cited By ~ 30

Author(s):

Gaurav Raj Dwivedi ◽

Anupam Maurya ◽

Dharmendra Kumar Yadav ◽

Feroz Khan ◽

Mahendra P. Darokar ◽

...

Keyword(s):

Drug Resistance ◽

Nalidixic Acid ◽

Ursolic Acid ◽

Reversal Potential ◽

Resistance Reversal

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Medicinal and Biological Significance of Phenoxazine Derivatives

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201214102151 ◽

2020 ◽

Vol 20 ◽

Author(s):

Jaya Dwivedi ◽

Neetu Yaduvanshi ◽

Shruti Shukla ◽

Sonika Jain

Keyword(s):

Drug Resistance ◽

Biological Significance ◽

Biological Application ◽

Pharmacological Activities ◽

Resistance Reversal ◽

Anti Inflammatory ◽

Pharmacological Application

: Since 1887, phenoxazine derivatives have attracted attention of chemist due to its versatile utility, industrially and pharmacologically. Literature is found abundant with various pharmacological activities of phenoxazine derivatives like antitumor, anticancer, antifungal, antibacterial, anti-inflammatory, anti-diabetic, anti-viral, anti-malarial, antidepressant, analgesic and many other drug resistance reversal activities. This review covers detailed over-view on pharmacological application of phenoxazine nucleus, its chemistry and reactivity and also illustrating the incorporation of different group at different positions enhancing its biological application, besides some synthetic procedures.

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Polyprodrug with Glutathione Depletion and Cascade Drug Activation for Multi-drug Resistance Reversal

Biomaterials ◽

10.1016/j.biomaterials.2020.120649 ◽

2021 ◽

pp. 120649

Author(s):

Xuan Xiao ◽

Kewei Wang ◽

Qingyu Zong ◽

Yalan Tu ◽

Yansong Dong ◽

...

Keyword(s):

Drug Resistance ◽

Glutathione Depletion ◽

Multi Drug Resistance ◽

Resistance Reversal ◽

Drug Activation

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Cisplatin Resistance Reversal of Lung Cancers by Tumor Acidity-Activable Vesicular Nanoreactors via Tumor Oxidative Stress Amplification

Journal of Materials Chemistry B ◽

10.1039/d0tb02876b ◽

2021 ◽

Author(s):

Jean Felix Mukerabigwi ◽

Yu Han ◽

Nannan Lu ◽

Wendong Ke ◽

Yuheng Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Drug Resistance ◽

Therapeutic Efficacy ◽

Cisplatin Resistance ◽

Clinical Applications ◽

Lung Cancers ◽

Resistance Reversal ◽

Tumor Acidity ◽

Stress Amplification ◽

Novel Strategy

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against a variety of cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing...

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