Antibacterial Profile of a Microbicidal Agent Targeting Tyrosine Phosphatases and Redox Thiols, Novel Drug Targets

The activity profile of a protein tyrosine phosphatase (PTP) inhibitor and redox thiol oxidant, nitropropenyl benzodioxole (NPBD), was investigated across a broad range of bacterial species. In vitro assays assessed inhibitory and lethal activity patterns, the induction of drug variants on long term...

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Main Authors: Kylie White (Author), Gina Nicoletti (Author), Hugh Cornell (Author)
Format: Book
Published: MDPI AG, 2021-10-01T00:00:00Z.
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001 doaj_e078e9d8eb0e40d2abacfbbd2a4a005c
042 |a dc 
100 1 0 |a Kylie White  |e author 
700 1 0 |a Gina Nicoletti  |e author 
700 1 0 |a Hugh Cornell  |e author 
245 0 0 |a Antibacterial Profile of a Microbicidal Agent Targeting Tyrosine Phosphatases and Redox Thiols, Novel Drug Targets 
260 |b MDPI AG,   |c 2021-10-01T00:00:00Z. 
500 |a 10.3390/antibiotics10111310 
500 |a 2079-6382 
520 |a The activity profile of a protein tyrosine phosphatase (PTP) inhibitor and redox thiol oxidant, nitropropenyl benzodioxole (NPBD), was investigated across a broad range of bacterial species. In vitro assays assessed inhibitory and lethal activity patterns, the induction of drug variants on long term exposure, the inhibitory interactions of NPBD with antibiotics, and the effect of plasma proteins and redox thiols on activity. A literature review indicates the complexity of PTP and redox signaling and suggests likely metabolic targets. NPBD was broadly bactericidal to pathogens of the skin, respiratory, urogenital and intestinal tracts. It was effective against antibiotic resistant strains and slowly replicating and dormant cells. NPBD did not induce resistant or drug-tolerant phenotypes and showed low cross reactivity with antibiotics in synergy assays. Binding to plasma proteins indicated lowered in-vitro bioavailability and reduction of bactericidal activity in the presence of thiols confirmed the contribution of thiol oxidation and oxidative stress to lethality. This report presents a broad evaluation of the antibacterial effect of PTP inhibition and redox thiol oxidation, illustrates the functional diversity of bacterial PTPs and redox thiols, and supports their consideration as novel targets for antimicrobial drug development. NPBD is a dual mechanism agent with an activity profile which supports consideration of tyrosine phosphatases and bacterial antioxidant systems as promising targets for drug development. 
546 |a EN 
690 |a antimicrobial 
690 |a nitropropenyl benzodioxole 
690 |a nitroalkenyl benzenes 
690 |a tyrosine signaling 
690 |a protein tyrosine phosphatase inhibitor 
690 |a thiol oxidant 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Antibiotics, Vol 10, Iss 11, p 1310 (2021) 
787 0 |n https://www.mdpi.com/2079-6382/10/11/1310 
787 0 |n https://doaj.org/toc/2079-6382 
856 4 1 |u https://doaj.org/article/e078e9d8eb0e40d2abacfbbd2a4a005c  |z Connect to this object online.