Farmacia

The present paper reports a new method for the synthesis of a Cu(II) ternary system using N,N'-bis[(4-methylphenyl)sulfonyl]ethylenediamine and 1,10-phenantroline as ligands. The binding of the complex to DNA was investigated by thermal denaturation. Its potency as artificial nuclease has also been tested and an efficient oxidative DNA cleavage was observed in the presence of a reducing agent (sodium ascorbate).

Heterocyclic compounds containing the 1,2,4-triazole ring and the thiazolo[3,2-b][1,2,4]triazole fused ring system in their structure have been reported to exhibit antibacterial, antifungal, anticancer, anti-inflammatory and analgesic activities. Considering this fact, the aim of this study was the synthesis and characterization of novel thiazolo[3,2-b][1,2,4]triazole derivatives and their corresponding acyclic thioether intermediates, having different substituents which lead to anti-inflammatory activity. Thiazolo[3,2-b][1,2,4]triazole derivatives were obtained in a single step when the condensation between mercapto-triazoles and α-halogenocarbonyls was performed at reflux in acid catalysis, or via acyclic thioether intermediates, when the synthesis was performed at room temperature, in alkaline media. The synthesized compounds were purified and characterized by¹H NMR,¹³C NMR, IR and MS. Their biological potential concerning anti-inflammatory and analgesic activities will be investigated in further studies. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.

The esters (3a-f) and amides (4a-c) of 2-(3,4-dihydro-3-oxo-2H-[1,2,4] triazino[4,3-c]-quinazolin-4-yl)acetic acid were synthesized by prior esterification or aminolysis of the acid 2. The structure of the synthesized compounds was confirmed by spectroscopic investigations. Almost all substances, which have been tested in vitro for the antioxidant activity in nitrosative stress, have shown significant antioxidant activity in comparison with N-acetylcystein (N-ACC). Compound 3f revealed the best antioxidant properties in a nitrosative stress model. Few weeks after the implementation of the new legislation, it seems that its purpose has at least partially been achieved; a number of "dreams shops" closed or changed their field of activity. However, it is possible that some of the consumers of such products, which have rather moderate risks, will replace them with drugs associated with higher risks, acquired from the black market. Whether the general outcome would be positive or negative will remain to be seen.

In the context of the alarming incidence of the multidrug-resistant Candida sp. based infections, a new series of 1,2,4-triazole-3-yl-mercapto derivatives were synthesized and evaluated as potential antifungal agents. The affinity of the synthesized compounds towards the catalytic site of the lanosterol 14α-demethylase (CYP51) was evaluated in silico, by molecular docking studies. The antifungal activity of the titled compounds was evaluated in vitro against pathogenic strains of Candida sp., by measuring the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC). The data obtained from the docking simulation showed that the new synthesized compounds might act as non-covalent inhibitors of fungal CYP51. The results of the in vitro antifungal screening support their potential anti-Candida activity, compound 3b exhibiting a similar effect as fluconazole, used as antifungal reference drug. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.

In order to synthesize novel anti-inflammatory and analgesic compounds with reduced ulcerogenic risk, a series of thiazolo[3,2-b][1,2,4]triazoles (6a-6d) and their corresponding acyclic intermediates (5a-5d) bearing benzenesulfonamide moiety were obtained and characterized by spectral analysis (¹H NMR,¹³C NMR, IR and MS). All synthesized compounds were evaluated in vivo for their anti-inflammatory and antinociceptive activities in a rat model of acute inflammation induced by λ-carrageenan. The compounds 5b, 5c and 6d showed significant anti-inflammatory activity when compared to negative control group, but they did not show superior anti-inflammatory activity when compared to diclofenac, as reference drug. The compounds were also screened for antinociceptive activity in a model of inflammatory hyperalgesia and compounds 5a, 5b, 5c, 6a, 6d presented a significant increase of nociceptive threshold in the inflamed paw. Moreover, compounds 5c, 6a, 6b, 6c and 6d did not show any significant ulcerogenic activity. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.

The purpose of the present work was to select substituents by using Topliss modified approach to synthesize new 1,3 oxazines with antimicrobial effect. In the series of 6-[4-substitutedphenyl]-4-phenyl-6H-1,3-oxazin-2-amines and N-[6-(4-substitutedphenyl)-4-phenyl-6H-1,3-oxazinyl] acetamides, substituents at fourth position of the phenyl ring were selected according to the Topliss modified approach and the initial set of compounds was synthesized. The antimicrobial screening revealed that compounds with methoxy substituent having negative sigma (-0.04) and negative pi (-0.27) values are good antimicrobial agents showing low minimum inhibitory concentration (MIC). The hydroxyl group substituent with more negative sigma (-0.61) and pi (-0.37) values was selected to synthesize final set compounds and were found better antimicrobials than the initial set of compounds. The study revealed that electron donating polar substituents at fourth position of the phenyl ring are required to improve antimicrobial potential in the series of 6-[4-substitutedphenyl]-4-phenyl-6H-1,3-oxazin-2-amines and N-[6-(4-substitutedphenyl)-4-phenyl-6H-1,3-oxazinyl] acetamides.

This study presents the synthesis and evaluation of the analgesic effect of 1,3-thiazolidin-4-one derivatives. Tested compounds were prepared by the cyclization reaction of appropriate N-substituted carboxylic acid hydrazide derivatives with mercaptoacetic acid. The purpose of this study was the evaluation of the analgesic properties of 1,3-thiazolidin-4-one derivatives. In addition to this, we tried to explain the role of serotonin receptors in the antinociceptive mechanisms of tested compounds. The experiments were carried out using male Albino Swiss mice (20-25g). The compounds were administered intraperitoneally (ip) and were analysed for analgesic activities in models of pain in mice. Additionally, they were tested for safety on the central nervous system of mice in selected behavioural tests. Our results revealed an interesting analgesic activity of the tested compounds. The tested derivatives showed low toxicity, reflected by their LD 50 value. Moreover, none of these compounds exhibited neurotoxic properties or impaired the cognitive activity of mice, even at the highest doses used. All tested derivatives showed analgesic activity. Among the tested compounds, N-[2-(4-methylphenyl)-4-oxo-1,3-thiazolidin- 3-yl] acetamide seems to be the most effective painkiller. It has a pronounced antinociceptive effect towards thermal and mechanical pain stimulation. The present results support the idea that 5-HT receptors play an important role in the control of pain. The compounds that modulate 5-HT receptors activity may have clinical utility in pain therapy. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.

A new series of phthalimide based 15-lipoxygenase-1 inhibitors were synthesized and their cytotoxic potency was also evaluated in three cancerous cell lines. Namely, SKNMC (neuroblastoma), PC3 (prostate carcinoma) and HT29 (colorectal cancer) cell lines were applied and the obtained results were compared to doxorubicin. The obtained compounds exhibited a high inhibitory activity towards 15-lipoxygense-1 compared to quercetin as reference drug. Compound 3e with meta methoxy moiety was the most efficient one in this series (IC50 = 1.96 ± 0.2 nM). An acceptable in vitro anticancer activity was also observed especially against HT29 cell line. Compound 3d with ortho methoxy moiety demonstrated the highest cytotoxic effect against the mentioned cell line (IC50 = 80.1 nM). The most probable binding mode of the final compounds was also explored using molecular docking. © 2017, Romanian Society for Pharmaceutical Sciences. All rights reserved.

A novel series of binuclear complexes of the [M2L(AcO)(2)(H2O)(4)] type, where M= Cu(II), Ni(II), Co(II) or Mn(II) and L= (C39H34N4O6)(2-), were synthesized by template condensation of 1,3-bis(2'-formylphenyl)-1,3-dioxapropane, L-tryptophan and metal acetate in methanolic medium. The complexes of M(II):L (2:1) type were characterized by elemental analyses, molar conductivity measurements, IR, electronic spectra and magnetic susceptibility measurements. The low value of molar conductivity indicates them to be non-electrolytes. Based on the magnetic and electronic spectral data, an octahedral / distorted octahedral geometry may be proposed for all the complexes. The new complexes were screened for their antimicrobial activity towards ten microbial strains, by qualitative and quantitative assays. Our results indicated that the [Cu2L(AcO)(2)(H2O)(4)] complex was the most active of the studied compounds, concerning both the intensity of the antimicrobial activity and the microbial spectrum.

The present research work was focused on the computational and pharmacological potential of 1,3,4-oxadiazole and pyrazole novel derivatives including: N-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methoxy]phenyl acetamide (a3), 5-[(naphthalen-2-yloxy) methyl]-1,3,4-oxadiazole-2-thiol (b3), 3-phenyl-5-(o-hydroxyphenyl)-1-[2-(p-N-acetylaminophenoxyacetylpyrazole (a6) and 3-phenyl-5-(o-hydroxy phenyl)-1-[2-(2’-naphthyloxy)acetyl] pyrazole (b6). Docking against targets including epidermal growth factor receptor (EGFR), tubulin, cyclooxygenase-2 (COX-2) and 5-lypoxygenase (5-LOX) were followed by the investigation of a3, b3, a6, and b6 for toxicity, tumour inhibition, free radical scavenging, analgesic and anti-inflammatory potential. Compound a3 showed binding and moderate inhibitory effects in all assays, b3 possess good affinity for COX-2 and 5-LOX which can be correlated to its highest analgesic and anti-inflammatory effects. Compound a6 showed binding to all targets and antioxidant potential, with an EC50 value of 100 µg/mL, b6 formed two hydrogen bonds with tubulin and was the most potent in the toxicity assessment and tumour inhibition with LC50 values of 2.47 and 5.51 µg/mL respectively. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.

Some 2-R-5-formyl-1,3,4-thiadiazole derivatives have been synthesized and characterized by their spectral data. Thus, the present paper describes the formation and hydrolysis, through Sommelet reaction, of some hexamethylenetetramine salts from which some new heterocyclic aldehydes resulted.

A series of 5-arylamino-1,3,4-thiadiazol-2-yl acetic acid esters have been synthesized by the cyclization of the corresponding thiosemicarbazides with concentrated sulphuric acid followed by the esterification of the amide group. The thiosemicarbazides derivatives were obtained by nucleophilic addition of cyanoacetic acid hydrazide to different arylisothiocyanates. The newly synthesized compounds were characterized by their physical parameters and the structures were elucidated by spectral data and elemental analysis.

A series of new 1,3,4-oxadiazole derivatives incorporating thiophene moiety were synthesized by the cyclization of N-(2-thenoyl)-N'-aroylhydrazine in the presence of phosphorus oxychloride. The intermediate and final compounds were characterized by infrared (IR), nuclear magnetic resonance (¹H-NMR and¹³C-NMR) spectroscopy, and by their physico-chemical properties. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.

Helicobacter pylori is a major human pathogen that causes gastric and extra-gastric complications and infects around 50% of the global population. Gastric cancer is a serious consequence of H. pylori infection. About 89% of all gastric cancers can be attributed to this pathogen. Treatment is indicated for all infected patients, as a strategy to knock down the risk of gastric malignancy. Due to the high level of antimicrobial resistance, new medicines are needed to treat H. pylori infection. This paper presents 2-amino-1,3,4-thiadiazole derivatives which exhibited anti-H. pylori effect. Some of the reported compounds showed higher activity compared to standard drugs, making the 2-amino-1,3,4-thiadiazole core a possible pattern for future anti-H. pylori agents. © 2020, Romanian Society for Pharmaceutical Sciences. All rights reserved.

A new series of 4-methyl-2-(pyridin-3-yl)-thiazole-5-yl-oxadiazolines were synthesized starting from 4-methyl-2-(pyridin-3-yl)thiazole-5-carbohydrazide. The newly synthesized compounds were characterized by analytical¹H-NMR,¹³C-NMR and mass spectral data. These compounds were screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial strains and one fungal strain (Candida albicans). © 2017, Romanian Society for Pharmaceutical Sciences. All rights reserved.

The 4-phenyl-1-[α-acylamino-β-(p-X-phenyl)]acriloyl thiosemicarbazides 3a-h were synthesized using 2-R-4-(p -X-benzylidene)-oxazol-5-ones 1a-h as starting materials. The reaction of compounds 1a-h with hydrazine hydrate led to the formation of acid hydrazides 2a-h. The thiosemicarbazide derivatives 3a-h were obtained by nucleophilic addition of corresponding acid hydrazides 2a-h to phenylisothiocyanate. The newly synthesized compounds structures were elucidated by spectral data and elemental analysis.

Cyclization of 4-phenyl-1-[α-acylamino-β-(p-X-phenyl)]acriloyl thiosemicarbazides 2a-h with concentrated sulfuric acid conduCted to 2-phenylamino-5-[(α-acylamino)-p-X-stiryl]-1,3,4-thiadiazole 3a-h. The newly synthesized compounds structures were elucidated by elemental analysis and spectral data.

Compounds bearing the 1,4-naphthoquinone ring and sulphur containing derivatives had been the subject of much interest due to their antimicrobial, antiviral, anti-inflammatory and anti-tumoural activities. Design of new derivatives of naphthoquinones, in order to improve their pharmaceutical properties, is still a research area of utmost importance. In the present study, we describe the synthesis, physico-chemical properties and evaluation of antimicrobial activity of new 2-mercapto-3-substituted-1,4-naphthoquinones. For the synthesis we used different 2-chloro-3-substituted-1,4-naphthoquinones and thiourea. The new naphthoquinone derivatives were characterized by elemental analysis, UV-VIS and IR spectrometry, mass spectrometry and 1H–NMR. All this methods confirmed the structure of the compounds. The antimicrobial activity was tested on several Gram-positive and Gram-negative bacteria using disk diffusion technique. In general, the compounds were active against tested Gram-positive bacteria. This encourages further studies for application of these compounds as antibiotic therapy. © 2015, Romanian Society for Pharmaceutical Sciences. All rights reserved.

The present work reports the synthesis, physico-chemical, spectral characterization and molecular docking study of a novel series of 1,4-phenylene-bisthiazoles. The newly synthesized 1,4-phenylene-bisthiazole derivatives were obtained with good yields through a Hantzsch condensation reaction between the thioamide intermediate and various alfa-haloketones or alfa-haloesters. The proposed structure of the compounds was confirmed by quantitative elemental analysis and spectral data: mass spectrometry and proton nuclear magnetic resonance. A molecular docking study was performed in order to investigate the potential binding affinity of the synthesized compounds towards the fungal lanosterol 14α-demethylase. The results of the molecular docking study showed that these compounds have potential antifungal activity and could be considered for further in vitro biological evaluation. © 2017, Romanian Society for Pharmaceutical Sciences. All rights reserved.