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In a basic medium, 5-Mercapto-1,2,4-triazoles pass into the thiol form, allowing their transformation into sodium salts, which, in reaction with sodium monochloroacetate, lead to sodium 5-thioacetates of 1,2,4-triazoles-3,4-disubstituted. Sulfur derivatives converted to pivalic mixed anhydrides were used as active forms in the acylation of 6-amino penicillanic acid (6-AP) to obtain new semisynthetic penicillins. They contain in the molecule, together with the β-lactam ring, the nucleus 3-[(5-nitroindazol-1′-yl-methyl)]-4-aryl-5-mercapto-1,2,4-triazole, both contributing to an important antibacterial effect. The structure of the new antibiotics was confirmed by the results of elemental and spectral analysis (FT-IR, 1H- and 13C-NMR). The synthetic penicillins were tested for toxicological action and antibacterial activity and the obtained results were close to those for amoxicillin, the reference drug.

Bacterial oral diseases are chronic, and, therefore, require appropriate treatment, which involves various forms of administration and dosing of the drug. However, multimicrobial resistance is an increasing issue, which affects the global health system. In the present study, a commercial amphiphilic copolymer, Pluronic F127, was used for the encapsulation of 1-(5′-nitrobenzimidazole-2′-yl-sulphonyl-acetyl)-4-aryl-thiosemicarbazide, which is an original active pharmaceutical ingredient (API) previously synthesized and characterized by our group, at different copolymer/API weight ratios. The obtained micellar systems, with sizes around 20 nm, were stable during 30 days of storage at 4 °C, without a major increase of the Z-average sizes. As expected, the drug encapsulation and loading efficiencies varied with the copolymer/API ratio, the highest values of 84.8 and 11.1%, respectively being determined for the F127/API = 10/1 ratio. Moreover, in vitro biological tests have demonstrated that the obtained polymeric micelles (PMs) are both hemocompatible and cytocompatible. Furthermore, enhanced inhibition zones of 36 and 20 mm were observed for the sample F127/API = 2/1 against S. aureus and E. coli, respectively. Based on these encouraging results, it can be admitted that these micellar systems can be an efficient alternative for the treatment of bacterial oral diseases, being suitable either by injection or by a topical administration.

In order to obtain new substances with potential biological activity dipeptide derivatives from p-aminobenzoyl-phenylglycine and p-aminobenzoyl-phenylalanine were grafted on 1,2,4-triazolic heterocycle. The new synthesized compounds belong to the group of antimetabolites, group used in medicine for treating malignant tumors. Also, it is possible to study the correlation between chemical structure and biological activity of the new compounds.

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives’ applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and 1H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against Mycobacterium tuberculosis.

Dipeptide derivatives from p-aminobenzoyl-phenylglycine and p-aminobenzoyl-phenylalanine were grafted on 1,2,4-triazole heterocycle in order to get new substances with potential biological activity...

International audience; New polymer-bioactive compound systems were obtained by immobilization of triazole derivatives onto grafted copolymers and grafted copolymers carrying betaine units based on gellan and N-vinylimidazole. For preparation of bioactive compound, two new types of heterocyclic thio-derivatives with different substituents were combined in a single molecule to increase the selectivity of the biological action. The 5-aryl-amino-1,3,4 thiadiazole and 5-mercapto-1,2,4-triazole derivatives, each containing 2-mercapto-benzoxazole nucleus, were prepared by an intramolecular cyclization of thiosemicarbazides-1,4 disubstituted in acidic and basic medium. The structures of the new bioactive compounds were confirmed by elemental and spectral analysis (FT-IR and 1H-NMR). The antimicrobial activity of 1,3,4 thiadiazoles and 1,2,4 triazoles was tested on gram-positive and gram-negative bacteria. The triazole compound was chosen to be immobilized onto polymeric particles by adsorption. The Langmuir, Freundlich, and Dubinin–Radushkevich adsorption isotherm were used to describe the adsorption equilibrium. Also, the pseudo-first and pseudo-second models were used to elucidate the adsorption mechanism of triazole onto grafted copolymer based on N-vinylimidazole and gellan (PG copolymer) and grafted copolymers carrying betaine units (PGB1 copolymer). In vitro release studies have shown that the release mechanism of triazole from PG and PGB1 copolymers is characteristic of an anomalous transport mechanism.

New di-(β-chloroethyl)-amides of some acids derived from 2-mercaptobenzoxazole were prepared by reaction of the corresponding pivalic mixed anhydrides with di-(β-chloroethyl)-amine. A study regarding the optimization of the chemical reactions was made for the case of di-(β-chloroethyl)-amines. The quantum chemical analysis by Spartan’14 was made in order to establish the most stable configuration of the ground electronic states for the obtained chemical structures and some physico-chemical parameters of N-mustards reported in this paper. Mercaptobenzoxazoles substituted in the side chain with the cytotoxic group show antitumor activity and they inhibit Ehrlich Ascites in an appreciable proportion compared to the drug I.O.B.-82, as our studies evidenced.

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of N-vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/N,N,N&prime, N&prime, tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: ci = 0.08 mol/L, cm = 0.8 mol/L, cp = 8 g/L, tr = 4 h and T = 50 &deg, C. The kinetics of the graft copolymerization of N-vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, 1H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.

Amidic compounds, derivatives of the 5-nitro-benzimidazolyl-2-mercapto-acetic acid were obtained in order to get new cytostatic substances. Two azotyperitic derivatives were obtained by the grafting of the di-(b-chloroethyl)-amine group on molecules of two of the amidic compounds. The NMR and FT-IR spectra confirmed the structure of the new compounds. The mitodepresive action of the new compounds has been tested on root meristems of Lepidiumm sativum L.

Porous microparticles of chitosan- g -poly(glycidyl methacrylate) were obtained by grafting chitosan onto crosslinked networks based on glycidyl methacrylate and ethylene glycol dimethacrylate using suspension polymerization technique. A new cephalosporin from the indazole class prepared by acylation of 7-Aminodesacetoxycephalosporanic acid with mixed anhydride of 5-nitroindazole-1-yl-acetic acid was used as active principle. The cephalosporin-microparticle systems were characterized by FT-IR spectroscopy, SEM and AFM analysis. Batch experiments were carried out to study the influence of initial drug concentration, temperature, contact time, drug:microparticles ratio and pH on the adsorption process of cephalosporin onto porous crosslinked microparticles. Two-parameter and three-parameter isotherm models were used to evaluate the adsorption equilibrium. The values of diffusion coefficients indicate that the cephalosporin adsorption onto microparticles was controlled by both film diffusion and pore diffusion mechanisms. The analysis of the kinetic data of the release process indicate that the release mechanism of cephalosporin from microparticles corresponds to the anomalous transport mechanism.

Two derivatives of glutamine were synthesized and the most convenient physical conditions for obtaining reactions were established in factorial experiments with temperature and time of reactions considered as relevant variables. A quantum-mechanical characterization for the new compounds was performed by using HyperChem 8.0.6 Programs and their physical and chemical properties were theoretically estimated. The toxicity of two new compounds was experimentally determined.

Recently, it has been reported that the compounds bearing a sulfonamide moiety possess many types of biological activities, including antimicrobial activity. The synthesis of new sulfonamides obtained by condensation of 5-nitroindazole with the sulphochlorides of some methyl esters of substituted phenoxyacetic acid, toxicological evaluation of some synthesized 5-nitroindazole sulfonamides and their potential antimicrobial activity were discussed in this paper. The conditions in which the reactions take place with the highest yield were established. The optimization reactions were realized in a 32 factorial experiment. Some physico-chemical properties of the new synthesized compounds were theoretically established by using Spartan'14. The chemical structure of the synthesized compounds was confirmed through elemental and spectral (FT-IR and 1H-NMR) means. Toxicological tests show that sulfonamides derived from 5-nitroindazole are compounds with antimicrobial activity.

International audience; The aim of this research was the synthesis of novel 2,3-disubstituted 1,3 thiazolidines, derived from 5- nitroindazole with antimicrobial activity and their encapsulation into polymer nanocapsules. Starting from previously synthesised hydrazones, there have been obtained novel thiazolidines by reaction with thioglycolic acid. The envisaged chemical structures were confirmed by spectral and elemental analysis. Two of the obtained thiazolidines were encapsulated into cationic Eudragit E100 nanocapsules, obtained by nanoprecipitation. In order to enhance drug release characteristics and particle stability, Eudragit E100 nanocapsules were covered with anionic polysaccharide (sodium alginate), thus forming a complex polyelectrolyte based membrane. The obtained nanocapsules presented a slower and more controlled drug release. The synthesized active principles, in free state and encapsulated into polymer nanocapsules, were tested for their acute toxicity and their influence on the development of model bacterial strains (Staphylococcus mutans, Actinobacillus actinomycetemcomitans, Bacillus subtilis, Bacillus cereus, Salmonella enteritidis, Escherichia coli and Staphylococcus aureus).

The direct pharmacological properties of amino acids and the possibility of using them as carriers for other active pharmacological substances are well known. Methionine, being able to yield the methyl group, is very important in the treatment of hepatic diseases. Paracetamol acute poisoning causes liver injury in both humans and animals. The study is designed to synthesize some new methionine derivatives and toestablish a possible correlation between the new structure and the pharmacological properties. To this end, acute experimental poisoning with Panadol® (paracetamol) was performed while, for the treatment of liver injury caused by this compound, two original synthesis derivatives of methionine, namely N-(m-nitrobenzoyl)- L-methionine and N-(m-aminobenzoyl)-L-methionine, were used. Male Wistar rats were administeredPanadol® (paracetamol) per oral (7500 mg/kg). N-(m-nitrobenzoyl)-L-methionine (m-NBM) 50 mg/kg andN-(m-aminobenzoyl)-L-methionine (m-ABM) 50 mg/kg were given intraperitoneally, 30 minutes after Panadol® administration. Biochemical parameters such as SGOT, SGPT, serum bilirubin and glycemia were estimated to assess the liver function. Panadol® (paracetamol) poisoning produced an increase in serum transaminases, bilirubin and glicemia. These effects were reduced by treatment with m-NBM and especially m-ABM. These biochemical observations were supplemented by histopathological examination of liver sections. The results obtained with m-ABM were comparable with those reported on methionine, which is a recognised antidote in paracetamol poisoning.

Little references actually exist on neutralization therapy which could constitute the missing ring from an efficient treatment. As structural model capable to interact with organophosphoric substances, at the level of phosphor (P) atom, the common chemical element of the hole class of substances, was proposed those of benzimidazole. Different quantities of benzimidazole were put in contact with a fix quantity of trichlorphon in acid conditions and formation of a new compound was evidentiated by infrared spectrometry. Similar experiments were made utilizing benzimidazole derivatives (2 methyl or 2 benzyl benzimidazole) and different temperatures: 35°C and 40°C. By increasing massic rate: benzimidazole/triclorfon as well an increased reaction temperature, have favourably influenced trichlorphon capture. The obtained results justified an continuation of researches in the direction of new compounds with a structure similar with that of benzimidazole for funding an efficient neutralization therapy for organophosphoric substances.