Undesirable effects of chemical inhibitors of NAD(P)+ transhydrogenase on mitochondrial respiratory function

Bicego, Rafaela; Francisco, Annelise; Ruas, Juliana S.; Siqueira-Santos, Edilene S.; Castilho, Roger F.

doi:10.1016/j.abb.2020.108535

Cited by 7 publications

(2 citation statements)

References 73 publications

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“…NBD-Cl (4-chloro-7-nitrobenzofurazan) was used as a control because it provides measurable CC 50 after 24 h and is routinely used in our laboratory for cytotoxicity measures. This control reduces cells viability by inhibiting the ATP production of eukaryotic cells, including human and bovine cells [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment of Staphylococcus aureus-Associated Bovine Mastitis

Millette,

Lacasse,

Binette

et al. 2023

Antibiotics

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Staphylococcus aureus is one of the major pathogens causing bovine mastitis, and antibiotic treatment is most often inefficient due to its virulence and antibiotic-resistance attributes. The development of new antibiotics for veterinary use should account for the One Health concept, in which humans, animals, and environmental wellbeing are all interconnected. S. aureus can infect cattle and humans alike and antibiotic resistance can impact both if the same classes of antibiotics are used. New effective antibiotic classes against S. aureus are thus needed in dairy farms. We previously described PC1 as a novel antibiotic, which binds the S. aureus guanine riboswitch and interrupts transcription of essential GMP synthesis genes. However, chemical instability of PC1 hindered its development, evaluation, and commercialization. Novel PC1 analogs with improved stability have now been rationally designed and synthesized, and their in vitro and in vivo activities have been evaluated. One of these novel compounds, PC206, remains stable in solution and demonstrates specific narrow-spectrum activity against S. aureus. It is active against biofilm-embedded S. aureus, its cytotoxicity profile is adequate, and in vivo tests in mice and cows show that it is effective and well tolerated. PC206 and structural analogs represent a promising new antibiotic class to treat S. aureus-induced bovine mastitis.

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Section: Resultsmentioning

confidence: 99%

Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment of Staphylococcus aureus-Associated Bovine Mastitis

Millette,

Lacasse,

Binette

et al. 2023

Antibiotics

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show abstract

“…NNT control of mitochondrial matrix redox levels is especially important in LMRS catabolism. Specifically, NNT is potently inhibited by saturated fatty acid CoA thioesters, the primary matrix form of these fatty acids [ 93 , 94 , 95 ]. Thus, if levels of saturated fatty acids (especially palmitate and stearate) are elevated in the matrix as a result of desaturation failure in the absence of adequate cytosolic oxygen levels ( Section 3.3 ), mitochondrial matrix H 2 O 2 levels are expected to show an additional increase, suppressing further fatty acid import and catabolism (above).…”

Section: Detailed Description Of the Steps In The Lmrs Hypothesismentioning

confidence: 99%

Toward a Unifying Hypothesis for Redesigned Lipid Catabolism as a Clinical Target in Advanced, Treatment-Resistant Carcinomas

Bingham,

Zachar

2023

IJMS

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We review extensive progress from the cancer metabolism community in understanding the specific properties of lipid metabolism as it is redesigned in advanced carcinomas. This redesigned lipid metabolism allows affected carcinomas to make enhanced catabolic use of lipids in ways that are regulated by oxygen availability and is implicated as a primary source of resistance to diverse treatment approaches. This oxygen control permits lipid catabolism to be an effective energy/reducing potential source under the relatively hypoxic conditions of the carcinoma microenvironment and to do so without intolerable redox side effects. The resulting robust access to energy and reduced potential apparently allow carcinoma cells to better survive and recover from therapeutic trauma. We surveyed the essential features of this advanced carcinoma-specific lipid catabolism in the context of treatment resistance and explored a provisional unifying hypothesis. This hypothesis is robustly supported by substantial preclinical and clinical evidence. This approach identifies plausible routes to the clinical targeting of many or most sources of carcinoma treatment resistance, including the application of existing FDA-approved agents.

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NADPH supply and the contribution of NAD(P)+ transhydrogenase (NNT) to H2O2 balance in skeletal muscle mitochondria

Figueira

Francisco

Ronchi

et al. 2021

Archives of Biochemistry and Biophysics

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Undesirable effects of chemical inhibitors of NAD(P)+ transhydrogenase on mitochondrial respiratory function

Cited by 7 publications

References 73 publications

Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment of Staphylococcus aureus-Associated Bovine Mastitis

Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment of Staphylococcus aureus-Associated Bovine Mastitis

Toward a Unifying Hypothesis for Redesigned Lipid Catabolism as a Clinical Target in Advanced, Treatment-Resistant Carcinomas

NADPH supply and the contribution of NAD(P)+ transhydrogenase (NNT) to H2O2 balance in skeletal muscle mitochondria

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