Attractive S⋯π and π-π interactions in the pyrazine-2-thiocarboxamide structure: Experimental and computational studies in the context of crystal engineering and microbiological properties

Chylewska, Agnieszka; Sikorski, Artur; Ogryzek, Małgorzata; Makowski, Mariusz

doi:10.1016/j.molstruc.2015.10.032

Cited by 18 publications

(8 citation statements)

References 42 publications

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“…Some of these compounds including pyrazine-2aminoxime (PAOX), pyrazine-2-thiocarboxamide (PTCA), and 2-amine-5-bromo-3-(methylamine)pyrazine (ABMAP) were previously investigated by our group. [23][24][25] In the discovery of biologically active compounds, there are several important issues such as structure, tautomerism, acidbase equilibrium, hydrophobicity, and membrane permeability. Knowledge of these properties allows the potential biological and therapeutic activities and behavior of compounds in the body or environment to be predicted.…”

Section: Introductionmentioning

confidence: 99%

When biomolecules meet 2-hydrazinopyrazine: from theory through experiment to molecular levels using a wide spectrum of techniques

et al. 2020

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Section: Introductionmentioning

confidence: 99%

When biomolecules meet 2-hydrazinopyrazine: from theory through experiment to molecular levels using a wide spectrum of techniques

et al. 2020

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“…S–aromatic interactions refer to noncovalent complexation between S-containing groups and aromatic groups. These interactions are common among small chemical structures − and in proteins. − Protein-based S–aromatic interactions are known as S–aromatic motifs, and they form on association of the Cys and Met side chains with those of Phe, Tyr, Trp, or His. Close to 40 years ago, it was noted in 21 proteins that contacts between S and aromatic C atoms are more common than expected. , Since then, a number of bioinformatic analyses (Table ) have exposed the high frequency of S–aromatic motifs, − including those involving cystine residues.…”

Section: Introductionmentioning

confidence: 99%

Modeling Protein S–Aromatic Motifs Reveals Their Structural and Redox Flexibility

Orabi

English

2018

J. Phys. Chem. B

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S-aromatic motifs are important noncovalent forces for protein stability and function but remain poorly understood. Hence, we performed quantum calculations at the MP2(full)/6-311++G(d,p) level on complexes between Cys (HS, MeSH) and Met (MeS) models with models of Phe (benzene, toluene), Trp (indole, 3-methylindole), Tyr (phenol, 4-methylphenol), and His (imidazole, 4-methylimidazole). The most stable gas-phase conformers exhibit binding energies of -2 to -6 kcal/mol, and the S atom lies perpendicular to the ring plane. This reveals preferential interaction with the ring π-system, except in the imidazoles where S binds edge-on to an N atom. Complexation tunes the gas-phase vertical ionization potentials of the ligands over as much as 1 eV, and strong σ- or π-type H-bonding supports charge transfer to the H-bond donor, rendering it more oxidizable. When the S atom acts as an H-bond acceptor (N/O-H···S), calibration of the CHARMM36 force field (by optimizing pair-specific Lennard-Jones parameters) is required. Implementing the optimized parameters in molecular dynamics simulations in bulk water, we find stable S-aromatic complexes with binding free energies of -0.6 to -1.1 kcal/mol at ligand separations up to 8 Å. The aqueous S-aromatics exhibit flexible binding conformations, but edge-on conformers are less stable in water. Reflecting this, only 0.3 to 10% of the S-indole, S-phenol, and S-imidazole structures are stabilized by N/O-H···S or S-H···O/N σ-type H-bonding. The wide range of energies and geometries found for S-aromatic interactions and their tunable redox properties expose the versatility and variability of the S-aromatic motif in proteins and allow us to predict a number of their reported properties.

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“…The studied pyrazine derivatives (Figure 1) have found many applications in clinical and biological practice. Pyrazinamide (PZA) is used as an antituberculosis drug [1][2][3], pyrazine-2-thiocarboxamide (PTCA) and pyrazine-2-amidoxime (PAOX) have been found to have antimycotic potential against Candida albicans [4][5][6][7][8], and bortezomib (BZM) is the only proteasome inhibitor used in the treatment of multiple myeloma [9][10][11]. However, the clinical use of these substances is limited mainly due to their side effects, which include rhabdomyolysis, skin eruptions, neutropenia, intestinal obstruction, or renal failure in patients undergoing treatment with PZA and BZM [12][13][14] or other reactions resulting from inappropriate preparation in the case of PAOX and PTCA [4].…”

Section: Introductionmentioning

confidence: 99%

Sensors to the Diagnostic Assessment of Anticancer and Antimicrobial Therapies Effectiveness by Drugs a with Pyrazine Scaffold

Domżalska

Dąbrowska

Chojnowski³

et al. 2022

Chemosensors

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Treatment with pyrazine derivatives—antituberculosis pyrazinamide (PZA), anticancer bortezomib (BZM), and antifungal pyrazine-2-amidoxime (PAOX) and pyrazine-2-thiocarboxamide (PTCA)—is associated with side effects, as observed in the case of other therapeutic drugs. To prevent the side effects of pyrazine derivatives, researchers are working to develop a universal method that will detect these compounds in body fluids. There is a lack of literature data about voltammetric measurements with poly-L-amino acid-modified GCEs surfaces. The available reports describe the application of various modifications of these electrodes for the detection of different active substances of drugs; however, they do not indicate one particular method for the detection of drugs with a pyrazine skeleton. This research aimed to prepare three types of glassy carbon electrodes (GCEs) with modified surfaces by electropolymerization using 1, 10, and 100 mM solutions of L-glycine (Gly), L-alanine (Ala), L-lysine (Lys), respectively. The poly-amino acid coatings applied on GCE surfaces were analyzed in detail under a three-dimensional (3D) microscope and were used as chemosensors of four pyrazine drugs in stoichiometric tests. The results were compared with the measurements made on an unmodified GCE. To obtain reliable results, the linearity of measurements was also verified in the concentration gradient and appropriate scanning speed was chosen to achieve the most accurate measurements.

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Attractive S⋯π and π-π interactions in the pyrazine-2-thiocarboxamide structure: Experimental and computational studies in the context of crystal engineering and microbiological properties

Cited by 18 publications

References 42 publications

When biomolecules meet 2-hydrazinopyrazine: from theory through experiment to molecular levels using a wide spectrum of techniques

When biomolecules meet 2-hydrazinopyrazine: from theory through experiment to molecular levels using a wide spectrum of techniques

Modeling Protein S–Aromatic Motifs Reveals Their Structural and Redox Flexibility

Sensors to the Diagnostic Assessment of Anticancer and Antimicrobial Therapies Effectiveness by Drugs a with Pyrazine Scaffold

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