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August 2023


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DNA-binding study and nuclease activity induced by a copper(II), N,N'-bis[(4-methylphenyl)sulfonyl] ethylenediamine and 1,10-phenantroline ternary system

November 2008


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M. Bojitǎ
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).

Synthesis of 2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3-c]quinazolin-4-yl) acetic acid derivatives as potential antioxidants in nitrosative stress model

March 2010


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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.

Figure 1. Synthesis of 1,2,4-triazole-3-yl-mercapto derivatives i. R1-N=C=S/EtOH abs./reflux; ii.TEA/EtOH abs./ reflux; iii. X-CH2-CO-R2/KOH/MeOH:DMF 1:1
Design and synthesis of some novel 1,2,4-triazole-3-yl-mercapto derivatives as potential anti-candida agents
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December 2018


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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.

Heterocycles 46. Synthesis, characterization and biological evaluation of thiazolo[3,2-b][1,2,4]triazoles bearing benzenesulfonamide moiety

October 2018


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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.

Figure 1. The synthesis of 3-aryl-5-mercapto-1,2,4-triazole derivatives. Reaction conditions: I. HCl 36.5%, KSCN, reflux 3 h; II. 1. NaOH 10%, reflux 3 h, 2. CH 3 COOH conc. [15, 27] The synthesis of the thiazolo[3,2-b][1,2,4]triazole derivatives is described in Figure 2 [15, 27-29]. The first route (route A) consists in the condensation of mercapto-triazoles 1-4 with different α-halogenoketones (phenacyl bromides, chloroacetone or ethyl 2-chloracetoacetate). The alternative pathway (route B) involves the formation and isolation of the imino thioether intermediates, which are cyclized in a further step, by treating with concentrated sulfuric acid, at room temperature [12, 24, 28].
Figure 2. The synthesis of the thiazolo[3,2-b][1,2,4]triazole derivatives and their imino thioether intermediates (route A: absolute ethanol, H 2 SO 4 conc., reflux 2 -30 h; route B: I. absolute ethanol, NaHCO 3 , room temperature, 24 -48 h; II. H 2 SO 4 conc., 2 -12 h)
Heterocycles 42. Synthesis and characterization of new thiazolo[3,2-b] [1,2,4]triazole derivatives with anti-inflammatory potential

January 2018


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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.

Synthesis, characterization and biological activity of CU(II), NI(II), CO(II) and MN(II) binuclear complexes derived from 1,3-BIS(2’-formylphenyl)-1,3-dioxapropane and L-tryptophan

January 2015


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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.

Substituent selection for design and synthesis of antimicrobial 1,3 oxazines: A topliss modified approach

January 2012


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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.

Figure 2. Structure of compound 3e (m-OCH 3 ) into the active site of 15-lipoxygenase-1 (pdb code: 1N8Q). Two hydrogen bonding interactions between oxygen atom of the methoxy group as well as nitrogen atom of the ligand and amino group of the Ile 857 has been detected. Ligand and Ile 857 has been represented as cylindrical and wireframe respectively. 
Discovery of 2-(1,3-dioxoisoindolin-2-yl)-n-phenylacetamide derivatives as probable 15-lipoxygenase-1 inhibitors with potential anticancer effects

January 2017


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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.

The analgesic effect of 1,3-thiazolidin-4-one derivatives as potential modulators of the serotoninergic system

March 2019


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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.

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