Synthesis and antiglycation activity of 3-phenacyl substituted thiazolium salts, new analogs of Alagebrium.

After preliminary ab initio calculations, 3-phenacyl substituted thiazolium salts, analogs of Alagebrium, were synthesized and investigated in vitro as glycation reaction inhibitors. The most part of investigations focused on the potential of the title compounds to attenuate the formation of fluorescent AGEs as well on their ability to disrupt the cross-linking formation among glycated proteins. Additionally, the capability of thiazolium salts to deglycate in the reaction of early glycation products with nitroblue tetrazolium was determined.

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-naphthalenylmethyl Derivatives of Uracil and Their Analogues As Probable Inhibitors of Human Cytomegalovirus Replication.

The synthesis of a new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing in position 3 naphthalen-1-yl-, naphthalen-2-yl-, 1-bromonaphthalen-2-ylmethyl, benzyl, and anthracene 9-methyl fragment was carried out. The antiviral properties of the synthesized compounds were studied against human cytomegalovirus. It was found that the compound that contained a bridge of five methylene groups has a high anti-cytomegalovirus activity in vitro.

Synthesis of 1-[ω-(Bromophenoxy)alkyl]-3-Naphthalenylmethyl Uracil Derivatives and Their Analogues as Probable Inhibitors of Human Cytomegalovirus Replication.

A new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing naphthalen-1-yl, naphthalen-2-yl, 1-bromonaphthalen-2-ylmethyl, benzyl, and anthracene-9-ylmethyl fragments in position 3 of uracil residue was synthesized. The antiviral properties of the synthesized compounds against human cytomegalovirus were studied. It was found that the compound containing a bridge consisting of five methylene groups exhibits a high anti-cytomegalovirus activity in vitro.

Guanidine Derivatives of Quinazoline-2,4(1,3)-Dione as NHE-1 Inhibitors and Anti-Inflammatory Agents.

Quinazolines are a rich source of bioactive compounds. Previously, we showed NHE-1 inhibitory, anti-inflammatory, antiplatelet, intraocular pressure lowering, and antiglycating activity for a series of quinazoline-2,4(1,3)-diones and quinazoline-4(3)-one guanidine derivatives. In the present work, novel N1,N3-bis-substituted quinazoline-2,4(1,3)-dione derivatives bearing two guanidine moieties were synthesized and pharmacologically profiled.

Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors.

The Na/H exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range.

Effects of Zoniporide and BMA-1321 Compound on the Rate of Oxygen Absorption by Cardiomyocyte Mitochondria in Rats with Experimental Chronic Heart Failure.

Uncoupling of respiration and ATP production by myocardial mitochondria was observed in rats with chronic isoproterenol intoxication (L-isoproterenol subcutaneously, 1 mg/kg, for 10 days) in comparison with controls (injected with the solvent). Inhibitors of NHE-1 zoniporide (1 mg/kg intraperitoneally, 13 days) and BMA-1321 compound (0.92 mg/kg intraperitoneally, 13 days) improved the mitochondrial function in rats with isoproterenol-induced cardiac failure: respiratory control coefficients increased, more so for the respiratory chain complex II, the main source of ROS in heart failure.

Synthesis and Antiviral Properties of 1-Substituted 3-[ω-(4-Oxoquinazolin-4(3H)-yl)alkyl]uracil Derivatives.

A series of uracil derivatives containing a 4-oxoquinazoline fragment bound to the nitrogen atom N3 of the pyrimidine ring by a short methylene bridge was synthesized to search for new antiviral agents. Some compounds in this series are shown to exhibit high inhibitory activity against human cytomegalovirus and the varicella zoster virus in a HEL cell culture.

The genus Toxoneura Macquart (Diptera, Pallopteridae) of the Oriental Region.

A new species of Toxoneura Macquart from Vietnam (Lai Châu province, Mt. Emei), T. gavryushini sp.

Contribution to the fauna of the genus Meroplius Rondani, 1874 (Diptera, Sepsidae) of the Australasian/Oceanian region.

Flies of the genus Meroplius Rondani, 1874 (Diptera: Sepsidae) of the Australasian and Oceanian regions, which includes 3 species, are reviewed. Generic and species descriptions and a key for the determination of species are given, and distribution data are summarized. One species, Meroplius timikana sp.

1-(4-Phenoxybenzyl) 5-Aminouracil Derivatives and Their Analogues - Novel Inhibitors of Human Adenovirus Replication.

Adenovirus infections are characterized by widespread distribution. The lack of causal therapy, which is effective in treating this group of diseases, explains the need for new therapeutic drugs. Notably, anti-adenoviral activity of [4-(phenoxy)benzyl]-5-(phenylamino)-6-azauracil, 1-[4-(phenoxy)benzyl]-5-(morpholino) uracil, 1-[4-(4-chlorophenoxy)benzyl]-5-(morpholino) uracil, and 1-[4-(4-fluorophenoxy)-benzyl]-5-(morpholino) uracil was observed.

Protective effect of magnesium acetyltaurate and taurine against NMDA-induced retinal damage involves reduced nitrosative stress.

Purpose: Retinal nitrosative stress associated with altered expression of nitric oxide synthases (NOS) plays an important role in excitotoxic retinal ganglion cell loss in glaucoma. The present study evaluated the effects of magnesium acetyltaurate (MgAT) on changes induced by N-methyl-D-aspartate (NMDA) in the retinal expression of three NOS isoforms, retinal 3-nitrotyrosine (3-NT) levels, and the extent of retinal cell apoptosis in rats. Effects of MgAT with taurine (TAU) alone were compared to understand the benefits of a combined salt of Mg and TAU.

Effect of Magnesium Acetyltaurate and Taurine on Endothelin1-Induced Retinal Nitrosative Stress in Rats.

Purpose: Retinal ganglion cell apoptosis in glaucoma is associated with elevated levels of endothelin-1 (ET1), a potent vasoconstrictor. ET1-induced retinal ischemia leads to altered expression of nitric oxide synthase (NOS) isoforms leading to increased formation of nitric oxide (NO) and retinal nitrosative stress. Since magnesium (Mg) is known to improve endothelial functions and reduce oxidative stress and taurine (TAU) possesses potent antioxidant properties, we investigated the protective effects of magnesium acetyltaurate (MgAT) against ET1-induced nitrosative stress and retinal damage in rats.

Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina.

Glutamate excitotoxicity plays a major role in the loss of retinal ganglion cells (RGCs) in glaucoma. The toxic effects of glutamate on RGCs are mediated by the overstimulation of N-methyl-D-aspartate (NMDA) receptors. Accordingly, NMDA receptor antagonists have been suggested to inhibit excitotoxicity in RGCs and delay the progression and visual loss in glaucoma patients.

[COMPARATIVE CEREBROPROTECTIVE EFFECT OF PREVENTIVE ADMINISTRATION OF MAGNESIUM HYDROXYBUTYRATE VERSUS MAGNESIUM SULFATE AND CAVINTON IN RATS WITH COMMON CAROTID ARTERY OCCLUSION].

Dose-dependent cerebroprotective effect of magnesium hydroxybutyrate (MHB) on common carotid artery occlusion model in rats was established. Administration of 150 mg/kg MHB led to significant decrease in animal mortality (up to 9.3 times) in comparison to control (p < 0.

Mechanism of the anticataract effect of liposomal MgT in galactose-fed rats.

Purpose: Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats.

Methods: The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging.

Exploration of acetanilide derivatives of 1-(ω-phenoxyalkyl)uracils as novel inhibitors of Hepatitis C Virus replication.

Hepatitis C Virus (HCV) is a major public health problem worldwide. While highly efficacious directly-acting antiviral agents have been developed in recent years, their high costs and relative inaccessibility make their use limited. Here, we describe new 1-(ω-phenoxyalkyl)uracils bearing acetanilide fragment in 3 position of pyrimidine ring as potential antiviral drugs against HCV.

1,6-Bis[(benzyloxy)methyl]uracil derivatives-Novel antivirals with activity against HIV-1 and influenza H1N1 virus.

A series of 1,6-bis[(benzyloxy)methyl]uracil derivatives combining structural features of both diphenyl ether and pyridone types of NNRTIs were synthesized. Target compounds were found to inhibit HIV-1 reverse transcriptase at micro- and submicromolar levels of concentrations and exhibited anti-HIV-1 activity in MT-4 cell culture, demonstrating resistance profile similar to first generation NNRTIs. The synthesized compounds also showed profound activity against influenza virus (H1N1) in MDCK cell culture without detectable cytotoxicity.

Comparison of the Efficiency of Adeprophen and Antidepressants of Various Groups on the Model of Reserpine-Induced Depression in Rats.

A new (aryloxyalkyl)adenine derivative Adeprophen (9-[2-(4-isopropylphenoxy)ethyl]adenine, VMA-99-82) has a strong antidepressant effect on the model of reserpine-induced depression in rats (single dose 4 mg/kg, intraperitoneally). This effect manifested in suppression of depression-like behavior in the Porsolt forced swimming test (shortening of immobility time and increase in immobility latency, number of jumping episodes, and time of active swimming) and sucrose consumption/preference test (increase in the consumption of 20% sucrose solution in g/100 g body weight and percentage of sucrose preference in relation to the total fluid preference). Adeprophen had a greater antidepressant effect than sertraline and fluoxetine, but was less potent than amitriptyline, imipramine, venlafaxine, and to a lesser extent to paroxetine.

Protective effect of magnesium acetyltaurate against endothelin-induced retinal and optic nerve injury.

Vascular dysregulation has long been recognized as an important pathophysiological factor underlying the development of glaucomatous neuropathy. Endothelin-1 (ET1) has been shown to be a key player due to its potent vasoconstrictive properties that result in retinal ischemia and oxidative stress leading to retinal ganglion cell (RGC) apoptosis and optic nerve (ON) damage. In this study we investigated the protective effects of magnesium acetyltaurate (MgAT) against retinal cell apoptosis and ON damage.

2-(2,4-Dioxy-1,2,3,4-Tetrahydropyrimidin-1-yl)-N-(4-Phenoxyphenyl)-Acetamides as a Novel Class of Cytomegalovirus Replication Inhibitors.

A series of novel uracil derivatives, bearing N-(4-phenoxyphenyl)acetamide moiety at N3 of a pyrimidine ring, has been synthesized. Their antiviral activity has been evaluated. It has been found that the novel compounds possess high inhibitory activity against replication of human cytomegalovirus (AD-169 and Davis strains) in HEL cell cultures.

A review of the genera Cleigastra Macquart, Gonarcticus Becker, Gonatherus Rondani, Hexamitocera Becker, Nanna Strobl, Orthacheta Becker and Spathephilus Becker (Diptera, Scathophagidae) of Russia.

Flies of the genera Cleigastra Macquart, 1835, Gonarcticus Becker, 1894, Gonatherus Rondani, 1856, Hexamitocera Becker, 1894, Nanna Strobl, 1894, Orthacheta Becker, 1894 and Spathephilus Becker, 1894 (all Scathophagidae) of the fauna of Russia are reviewed. Key to genera, generic descriptions and keys for determination of species are given, and data on geographical distribution are summarized. One species, Nanna cryophila sp.

A new species of the shore-fly genus Notiphila Fallén, 1810 (Diptera: Ephydridae) from Indonesia.

A new shore-fly species, Notiphila oksanae sp.n. from Indonesia is described.

5-Arylaminouracil Derivatives: New Inhibitors of Mycobacterium tuberculosis.

Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, and 1,3-di-(4'-hydroxy-2'-cyclopenten-1'-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-3-(4‴-hydroxy-2‴-cyclopenten-1‴-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M.