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Abstract

Several activators of soluble guanylate cyclase were investigated as potential inhibitors of rat liver mitochondrial monoamine oxidases (MAO) A and B. They all fitted into the previously designed "molds" of substrate-inhibitor binding sites of these enzymes. However, only two of them, NO donors (7-nitro-benzotetrazine-1,3-dioxide (7-NBTDO) and benzodifuroxan), caused nonselective inhibition of MAO A and MAO B with IC(50) values of 1.3-1.6 and 6.8-6.3 microM, respectively. The inhibitory effect on both MAO A and MAO B was reduced by mitochondria wash suggesting reversible mode of the enzyme inhibition. There was no correlation between potency of MAO inhibition and activation of human platelet soluble guanylate cyclase. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) had no effect on the manifestation of MAO inhibition by benzodifuroxan and 7-NBTDO; however, at 50 microM concentration carboxy-PTIO caused potent inhibition of MAO A with minor effect on MAO B activity. The data suggest that nonselective inhibition of MAO A and MAO B by benzodifuroxan and 7-NBTDO can be attributed to the properties of the chemical structures of these compounds. The results of the present study demonstrate a real possibility for the development of a new generation of effective reversible nonselective MAO inhibitors exhibiting equal inhibitory activity with respect to both MAO A and MAO B.

Fragmentation pathways analysis for the gas phase dissociation of protonated carnosine-oxaliplatin complexes

“…The endogenous dipeptide L-carnosine (β-alanyl-L-histidine) [1][2][3] is found in different body organs such as the stomach, kidney and at elevated levels in skeletal and cardiac muscles as well as in brain tissue in olfactory bulb and hippocampus. [4,5] Owing to its water solubility, carnosine levels are found to be particularly elevated in cytosolic cellular fractions.…”

Oxaliplatin complexes with carnosine and its derivatives: in vitro cytotoxicity, mass spectrometric and computational studies with a focus on complex fragmentation

“…[24] The endogenous dipeptide L-carnosine (β-alanyl-L-histidine) was discovered by Gulewitsch and Amiradzibi [25] from muscle tissue extracts in 1900 [26,27] and is found in several organs including the brain (olfactory bulb and hippocampus) [28], cardiac muscle, kidney and stomach. [29,30] In the skeletal muscle and nerve cells it is found at concentrations of up to 20 mM.…”

Benzofuroxan Derivatives as Potent Agents against Multidrug‐Resistant Mycobacterium tuberculosis

“…Previous studies have also demonstrated that Bfx derivatives interact with the thiol groups (À SH) present in the cysteine residues, often leading to enzymatic inhibition. [61,62] Therefore, we hypothesized that the Bfx nucleus could lead to the formation of a nitrous intermediate after biotransformation, which then served as an electrophilic site that would lead to the formation of an adduct after interaction with the cysteine residues (À SH) acting as nucleophiles.…”