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Bacterial cystathionine γ-lyase (bCSE) is the main producer of H2S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives.

Dopamine, adrenaline and octopamine are small polar molecules that play a vital role in regulatory systems. In this paper, phthalylglycyl chloride was proposed as a derivatization agent for octopamine, adrenaline and dopamine determination in urine for the first time. The derivatization procedure facilitated the use of reversed-phase liquid chromatography with positive electrospray ionization–high-resolution mass spectrometry. An LC-HRMS method was developed that provided quantification limits of 5 ng/mL and detection limits of 1.5 ng/mL for all analytes. The 95–97% yield of derivates was observed after a 10 min derivatization with phthalylglycyl chloride at pH 6.5 and 30 °C. The proposed method was successfully applied to the analysis of human urine samples. The obtained results were compared with those of conventional derivatization procedures with 9-fluorenyl-methoxycarbonyl chloride and dansyl chloride.

Macrocyclic glycopeptide antibiotics immobilized on silica are one of the effective classes of stationary phases for chiral recognition and HPLC separation of a wide range of optically active compounds. Enantioselectivity primarily depends on the chemical structure of the chiral ligand, immobilization chemistry, and separation conditions. In the present work, three new chiral stationary phases (CSPs) based on macrocyclic antibiotic eremomycin were prepared and investigated for enantioseparation of amino acids. Two eremomycin derivatives, including simple non-substituted amide and bulky adamantyl amide, provided important information on the role of the carboxylic group in the eremomycin structure in the chiral recognition mechanism concerning amino acid optical isomers. One more CSP having a chlorine atom in the same position elucidates the role of the first aromatic ring in the eremomycin structure as a crucial point for chiral recognition. CSP with immobilized chloreremomycin was the most successful among the phases prepared in this work. It was additionally investigated under various separation conditions, including the type and content of the organic solvent in the eluent, the effects of different additives, and the concentration and pH of the buffer. Importantly, an efficient enantioselective separation of amino acids was achieved with pure water as the eluent.

Heptose phosphates—unique linkers between endotoxic lipid A and O-antigen in the bacterial membrane—are pathogen-associated molecular patterns recognized by the receptors of the innate immune system. Understanding the mechanisms of immune system activation is important for the development of therapeutic agents to combat infectious diseases and overcome antibiotic resistance. However, in practice, it is difficult to obtain a substantial amount of heptose phosphates for biological studies due to the narrow scope of the reported synthetic procedures. We have optimized and developed an inexpensive and convenient synthesis for the first performed gram-scale production of 1-O-methyl d-glycero-α-d-gluco-heptoside 7-phosphate from readily available d-glucose. Scaling up to such amounts of the product, we have increased the efficiency of the synthesis and reduced the number of steps of the classical route through the direct phosphorylation of the O6,O7-unprotected heptose. The refined method could be of practical value for further biological screening of heptose phosphate derivatives.

A new series of conjugates of aminoadamantane and γ-carboline, which are basic scaffolds of the known neuroactive agents, memantine and dimebon (Latrepirdine) was synthesized and characterized. Conjugates act simultaneously on several biological structures and processes involved in the pathogenesis of Alzheimer’s disease and some other neurodegenerative disorders. In particular, these compounds inhibit enzymes of the cholinesterase family, exhibiting higher inhibitory activity against butyrylcholinesterase (BChE), but having almost no effect on the activity of carboxylesterase (anti-target). The compounds serve as NMDA-subtype glutamate receptor ligands, show mitoprotective properties by preventing opening of the mitochondrial permeability transition (MPT) pore, and act as microtubule stabilizers, stimulating the polymerization of tubulin and microtubule-associated proteins. Structure–activity relationships were studied, with particular attention to the effect of the spacer on biological activity. The synthesized conjugates showed new properties compared to their prototypes (memantine and dimebon), including the ability to bind to the ifenprodil-binding site of the NMDA receptor and to occupy the peripheral anionic site of acetylcholinesterase (AChE), which indicates that these compounds can act as blockers of AChE-induced β-amyloid aggregation. These new attributes of the conjugates represent improvements to the pharmacological profiles of the separate components by conferring the potential to act as neuroprotectants and cognition enhancers with a multifunctional mode of action.

A series of heterometallic carboxylate 1D polymers of the general formula [LnIIICd2(piv)7(H2O)2]n·nMeCN (LnIII = Sm (1), Eu (2), Tb (3), Dy (4), Ho (5), Er (6), Yb (7); piv = anion of trimethylacetic acid) was synthesized and structurally characterized. The use of CdII instead of ZnII under similar synthetic conditions resulted in the formation of 1D polymers, in contrast to molecular trinuclear complexes with LnIIIZn2 cores. All complexes 1–7 are isostructural. The luminescent emission and excitation spectra for 2–4 have been studied, the luminescence decay kinetics for 2 and 3 was measured. Magnetic properties of the complexes 3–5 and 7 have been studied; 4 and 7 exhibited the properties of field-induced single-molecule magnets in an applied external magnetic field. Magnetic properties of 4 and 7 were modelled using results of SA-CASSCF/SO-RASSI calculations and SINGLE_ANISO procedure. Based on the analysis of the magnetization relaxation and the results of ab initio calculations, it was found that relaxation in 4 predominantly occurred by the sum of the Raman and QTM mechanisms, and by the sum of the direct and Raman mechanisms in the case of 7.

Complexes [(dpp-BIAN)0CoIII2]·MeCN (I) and [(Py)2CoI2] (II) were synthesized by the reaction between cobalt(II) iodide and 1,2-bis(2,6-diisopropylphenylimino)acenaphthene (dpp-BIAN) or pyridine (Py), respectively. The molecular structures of the complexes were determined by X-ray diffraction. The Co(II) ions in both compounds are in a distorted tetrahedral environment (CoN2I2). The electrochemical behavior of complex I was studied by cyclic voltammetry. Magnetochemical measurements revealed that when an external magnetic field is applied, both compounds exhibit the properties of field-induced single ion magnets.

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both Mycobacterium tuberculosis and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential. Their synthesis and the results of the subsequent biological activity are reported herein.

A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7⁻67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28⁻61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50⁻60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20⁻50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20⁻50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls.

Here we report the synthesis and biological activity of new 5′-norcarbocyclic derivatives of bicyclic pyrrolo- and furano[2,3-d]pyrimidines with different substituents in the heterocyclic ring. Lead compound 3i, containing 6-pentylphenyl substituent, displays inhibitory activity with respect to a number of tumor cells with a moderate selectivity index value. Compound 3i induces cell death by the apoptosis pathway with the dissipation of mitochondrial potential.

Macrocyclic glycopeptide antibiotics immobilized on silica are one of the effective classes of stationary phases for chiral recognition and HPLC separation of a wide range of optically active compounds. Enantioselectivity primarily depends on the chemical structure of the chiral ligand, immobilization chemistry, and separation conditions. In the present work, three new chiral stationary phases (CSPs) based on macrocyclic antibiotic eremomycin were prepared and investigated for enantioseparation of amino acids. Two eremomycin derivatives, including simple non-substituted amide and bulky adamantyl amide, provided important information on the role of the carboxylic group in the eremomycin structure in the chiral recognition mechanism concerning amino acid optical isomers. One more CSP having a chlorine atom in the same position elucidates the role of the first aromatic ring in the eremomycin structure as a crucial point for chiral recognition. CSP with immobilized chloreremomycin was the most successful among the phases prepared in this work. It was additionally investigated under various separation conditions, including the type and content of the organic solvent in the eluent, the effects of different additives, and the concentration and pH of the buffer. Importantly, an efficient enantioselective separation of amino acids was achieved with pure water as the eluent. [ABSTRACT FROM AUTHOR]

A series of heterometallic carboxylate 1D polymers of the general formula [LnIIICd2(piv)7(H2O)2]n·nMeCN (LnIII = Sm (1), Eu (2), Tb (3), Dy (4), Ho (5), Er (6), Yb (7); piv = anion of trimethylacetic acid) was synthesized and structurally characterized. The use of CdII instead of ZnII under similar synthetic conditions resulted in the formation of 1D polymers, in contrast to molecular trinuclear complexes with LnIIIZn2 cores. All complexes 1–7 are isostructural. The luminescent emission and excitation spectra for 2–4 have been studied, the luminescence decay kinetics for 2 and 3 was measured. Magnetic properties of the complexes 3–5 and 7 have been studied; 4 and 7 exhibited the properties of field-induced single-molecule magnets in an applied external magnetic field. Magnetic properties of 4 and 7 were modelled using results of SA-CASSCF/SO-RASSI calculations and SINGLE_ANISO procedure. Based on the analysis of the magnetization relaxation and the results of ab initio calculations, it was found that relaxation in 4 predominantly occurred by the sum of the Raman and QTM mechanisms, and by the sum of the direct and Raman mechanisms in the case of 7. [ABSTRACT FROM AUTHOR]

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both Mycobacterium tuberculosis and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential. Their synthesis and the results of the subsequent biological activity are reported herein. [ABSTRACT FROM AUTHOR]

A series of novel 5′-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of Mycobacterium smegmatis was completely inhibited by the most active compounds at a MIC99 of 67 μg/mL (mc2155) and a MIC99 of 6.7–67 μg/mL (VKPM Ac 1339). Several compounds also showed the ability to inhibit the growth of attenuated strains of Mycobacterium tuberculosis ATCC 25177 (MIC99 28–61 μg/mL) and Mycobacterium bovis ATCC 35737 (MIC99 50–60 μg/mL), as well as two virulent strains of M. tuberculosis; a laboratory strain H37Rv (MIC99 20–50 μg/mL) and a clinical strain with multiple drug resistance MS-115 (MIC99 20–50 μg/mL). Transmission electron microscopy (TEM) evaluation of M. tuberculosis H37Rv bacterial cells treated with one of the compounds demonstrated destruction of the bacterial cell wall, suggesting that the mechanism of action for these compounds may be related to their interactions with bacteria cell walls. [ABSTRACT FROM AUTHOR]

Here we report the synthesis and biological activity of new 5′-norcarbocyclic derivatives of bicyclic pyrrolo- and furano[2,3-d]pyrimidines with different substituents in the heterocyclic ring. Lead compound 3i, containing 6-pentylphenyl substituent, displays inhibitory activity with respect to a number of tumor cells with a moderate selectivity index value. Compound 3i induces cell death by the apoptosis pathway with the dissipation of mitochondrial potential. [ABSTRACT FROM AUTHOR]