6-nitro-2-iminocoumarin 3-carboxylic acid 4-toluidide silver salt eliciting antibacterial activity
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to new compounds of coumarone class, namely, to 6-nitro-2-iminocoumarin 3-carboxylic acid 4-toluidide silver salt of the formula (1): that elicits an antibacterial effect and can be used in medicine. Invention provides preparing a new compound eliciting an antibacterial effect with respect to S. aureus, E. coli, and C. albicans with mononuclear cells values 0.25; 0.5 and 7.8 mcg/ml, respectively, and with acute toxicity value LD50 for these compounds 2 460 ± 230 mg/kg.
EFFECT: valuable properties of compound.
1 cl, 1 tbl, 2 ex
The invention relates to new biologically active compounds of class coumarins, particularly, to a silver salt of 4-toluidine 6-nitro-2-iminocoumarin-3-carboxylic acid of the formula (I)
exhibiting antimicrobial activity. The closest analogue to the structure of compound I is 2,4-xylidide 2-acetylaminofluorene-3-carboxylic acid (U.S. Pat. RU # 2193559 C1. Publ. 27.11.2002. Bull. No. 33) of the formula
having anticoagulant activity. As a benchmark comparison we have selected antimicrobial drugs dioxidine (Mashkovsky PPM Medicines. - M.: New wave, 2000, Vol.2, s-299) and fluconazole (ibid SS-362), widely used in medical practice.
The aim of the invention is the finding of new coumarin derivatives having antimicrobial activity.
This goal is achieved silver salt of 4-toluidine 6-nitro-2-iminocoumarin-3-carboxylic acid (II), which is obtained by the interaction of 5-nitrosalicylic aldehyde with 4-toluidino tsianuksusnogo acid formed at this 4-toluidin 6-nitro-2-iminocoumarin-3-carboxylic acid (II), is treated with an equivalent amount of silver nitrate.
The invention is illustrated by the following examples.
Example 1. 4-Toluidin 6-nitro-2-iminocoumarin-3-carboxylic acid (II). SMEs,67 g (0.01 mol) of 5-nitrosalicylic aldehyde, of 1.74 g (0.01 mol) 4-toluidine tsianuksusnogo acid, 5 drops of piperidine is boiled in 15 ml of ethanol for 1 h Precipitated after cooling the reaction mixture the precipitate was separated, washed with ether, and crystallized from dioxane. Get 2,98 g (92.3 per cent) II. So pl. 235-237°C. Found, %: With 63.4; H 4,3; N 13,2. With17H13N3O4. Calculated, %: From 63.1; H 4,0; N 13,0.
Example 2. The silver salt of 4-toluidine 6-nitro-2-iminocoumarin-3-carboxylic acid (I). Dissolving 0.32 g (0.001 mol) 4-toluidine 6-nitro-2-iminocoumarin-3-carboxylic acid in 80 ml of a mixture of isopropanol - dioxane (2:1) at low heat. To the warm solution with continuous stirring of the reaction mixture was added 0.17 g (0.001 mol) of silver nitrate in a minimum amount of water. The residue is filtered off, washed with alcohol on the filter and dried at room temperature. Obtain 0.25 g (58%) of compound I. T. pl.>300°C. Found, %: C Of 47.8; H 3,1; N and 10.0. C17H12N3O4Ag. Calculated, %: C 47,4; 2.8; N 9,8.
The structure of compounds I and II confirmed by the data of IR, PMR spectroscopy. In IR-spectra of compound I are the bands at 1670 cm-1(CO), 3310 cm-1(CONH). In the PMR spectra of compound I present: a singlet at 2,30 ppm (SN3), multiplet with the center of 7.60 ppm (M, aromatic rings).
The IR spectrum II exhibits bands at 1670 cm-1(CO), 3330 cm-1(=NH), 3420 cm (NH).
The claimed compound was tested for the presence he has antimicrobial activity.
Determination of the bacteriostatic activity was performed by the method of twofold serial dilutions in liquid nutrient medium (Manual on experimental (preclinical) study of new pharmacological substances. - M., 2000, s-273). For all the studied compounds were determined IPC in respect of pharmacopoeial strains: S.aureus was ATSS 6538-P, E. coli ATCC 25922, C. albicans ATCC 885-653, P. aeruginosa ATCC 9027. Crops produced in mesopotania broth, pH 7.0 with different concentrations of the tested compounds. The cultures were grown in test tubes on a beveled apparitional environment (mastopathy agar). To determine the antimicrobial activity was used 18-20-hour culture. For preparation of the working suspension of microbes produced washout grown culture isotonic solution of sodium chloride, and set the density of the microbial suspension according to the turbidity standard 5 units. Next, from the obtained microbial suspension (500 million MT/ml) were prepared working solution of bacteria with a concentration of 5 million MT/ml of This suspension of microbes was made in the amount of 0.1 ml in tubes with serial dilutions of study drug. Thus, microbial load when determining the ACA was 250000 MT/ml of the Studied compound in the amount of 0.05 g was dissolved in 5 ml of dimethyl who formamide; 1 ml of the prepared dilution of 1:100 was combined with 4 ml mycopathologia broth (1:500). Next was preparing a series of serial dilutions of the compounds twice with decreasing concentration.
Records of the results produced after 18-20 h of exposure control and experimental tubes in the incubator at 37 ° °C. Minimal inhibitory concentration (MIC) was determined by the absence of signs of microbial growth on nutrient medium: the last tube of stunting (clear broth) corresponds to the IPC of the drug in relation to this strain. Bacteriostatic effect of the studied compounds was compared with the action dioksidina (Adaska E.N., INF. and antimicrob, terap., 2001, No. 5, p.150-155). Antifungal activity was compared with the action of fluconazole (Rex J.Y., Walsh T.J., Sobel J.D. et all, Clin. Infect. Dis, 2000, V. 30, No. 4, R-678).
Acute toxicity (LD50) the claimed compounds was studied on white laboratory mice of both sexes weighing 19-20, Investigational compound was administered once in the stomach in the form of starch mucus in the amount of 1580, 2500, 3160 mg/kg, respectively, the observation of the animals was performed within 10 days. Statistical processing of results was carried out according to Prozorovsky CENTURIES (Prozorovsky CENTURIES, Prozorovsky BTW, Demchenko V.M. Pharmacol. and toxicol., 1978, No. 4, s-502).
The results are shown in the table.
As can be seen from the people, the connection I exceeds the activity dioxidine against S. aureus at least 250 times, E. coli is not less than 7.8 times, P. aeruginosa is not less than 250 times. The connection I also exceeds antifungal activity of fluconazole against C. albicans is not less than 2.1 times. Compound I according to the classification Izmerov NF (Izmerov NF Parameters toxicometric industrial poisons in a single, M.: Medicine, 1977, s) belongs to the class of moderately toxic substances.
Thus, a silver salt of 4-toluidine 6-nitro-2-iminocoumarin-3-carboxylic acid I shows a pronounced antimicrobial activity and is moderately toxic. Therefore, the claimed compound can be used in medicine as an antimicrobial drug.
Antimicrobial activity and acute toxicity of compounds I
|Connection||S.aureus, ug/ml||E. coli, ug/ml||.aeruginosa, ug/l||.albicans, ug/ml||LD50mg/kg|
The silver salt of 4-toluidine 6-nitro-2-iminocoumarin-3-carboxylic acid of the formula I
possessing antimicrobial activity.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to applying compounds of the formula (I) for preparing an antibacterial composition and veterinary composition eliciting with the enhanced activity.
EFFECT: valuable properties of agents.
4 cl, 3 tbl, 78 ex
FIELD: medicine, pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to compositions used for treatment and/or prophylaxis of chlamydium infections caused by C. pheumoniae. Pharmaceutical composition used for treatment and/or prophylaxis of chlamydium infection caused by C. pneumoniae comprises the taken phenolic compound, or extract, or fraction, or incomplete fraction comprising the taken phenolic compound or corresponding synthetic compound, or mixture of indicated compounds obtained from plants. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction obtained from plants and comprising indicated compound or corresponding synthetic compound on C. pneumoniae represents the definite percent of inhibition for formation of inclusions. The composition useful for health eliciting an anti-chlamydium effect with respect to C. pneumoniae comprises the taken phenolic compound or extract, or fraction, or incomplete fraction containing indicated compound or corresponding synthetic compound, or mixture of indicated compounds obtained from plants. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound obtained from plants on C. pneumoniae represents the definite percent for inhibition in formation of inclusions. Also, invention relates to applying the composition useful for health in preparing foodstuffs or as supplements for nutrition for every day. Also, invention relates to applying phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound or mixture of indicated compounds obtained from plants in manufacturing a medicinal agent used for treatment and/or prophylaxis of chlamydium infections caused by C. pneumoniae. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound obtained from plants on C. pneumoniae represents the definite percent in inhibition in formation of inclusions. Compositions promote to effective prophylaxis and treatment of chlamydium infections caused by C. pneumoniae.
EFFECT: valuable medicinal properties of compounds.
21 cl, 1 dwg, 1 tbl, 6 ex
FIELD: biotechnology, vaccines.
SUBSTANCE: vaccine comprises bacterial mass of Pasteurella multocida of serovariants A, B and D, Haemophilus pleuropneumonia of serogroups 1 and 2, and streptococcus of serogroups C and R, and also lysate-anigens of salmonellae Salmonella cholerae - suis, strain № 370 and Salmonella typhimurium № 415 mixed in the definite concentration. Vaccine elicits the high immunogenicity and provides the protection of pigs against infectious pneumonia of bacterial etiology and salmonellosis.
EFFECT: valuable veterinary properties of vaccine.
3 cl, 1 tbl, 5 ex
FIELD: veterinary science, infectious diseases.
SUBSTANCE: method involves applying furacyclin M as a tetracycline preparation and probiotic -ocarin additionally for 10 days that are given to calves from 12 old days age by the following schedule: furacyclin M in the dose 0.4-0.5 g/kg of body mass, 2 times per 24 h, and ocarin in the dose 8 x 106 bacterial cells, 1 time per 24 h before night. Invention promotes to enhancing functional activity of blood neutrophiles, elevating content of T- and B-lymphocytes and activating their function that, in turn, promotes to enhancing the natural resistance of calves body. Invention can be used for prophylaxis against chlamydia bronchopneumonia in calves.
EFFECT: improved method for prophylaxis.
5 tbl, 2 ex
FIELD: organic chemistry, medicine, phthisiology.
SUBSTANCE: invention proposes applying naphthoquinone derivatives for treatment and/or control of tuberculosis caused by Mycobacterium tuberculosis and a method for tuberculosis treatment. The claimed naphthoquinone derivatives are known as extracts from South Africa medicinal plants, for example, diospyrin and O-juglone. Indicated compounds are effective as against strains that are sensitive to M. tuberculosis and strains that are resistant to isoniazid and rifampicin or strains with the multiple resistance.
EFFECT: valuable medicinal properties of compounds.
7 cl, 2 tbl
FIELD: veterinary science.
SUBSTANCE: the method deals with injecting oxylate once daily for 3 d at the dosage of 1 ml/30 kg body weight at repeated therapy course in 5 d at the background of antibioticotherapy. The method enables to normalize biochemical and morphological blood values and increase average daily body weight gain in sick animals.
EFFECT: higher efficiency of therapy.
2 ex, 2 tbl
FIELD: biotechnology, molecular biology, medicine, genetic engineering, pharmacy.
SUBSTANCE: the hemopoietic protein comprises the amino acid sequence of the formula: R1-L1-R1, R2-L1-R1, R1-R2 or R2-R1 wherein R1 represents the modified ligand flt-3; R2 represents the modified human IL-3, the modified or unmodified colony-stimulating factor. Modification of R1 is carried out by addition of N-end with C-end directly or through linker (L2) that is able to join N-end with C-end to form new C- and N-ends. The modified human IL-3 is prepared by replacing amino acids at positions 17-123. The human G-CSF is modified by exchange of amino acids. The hemopoietic protein is prepared by culturing cells transformed with vector comprising DNA that encodes the hemopoietic protein. The hemopoietic protein stimulates producing hemopoietic cells and this protein is used as a component of pharmaceutical composition used in treatment of humans suffering with tumor, infectious or autoimmune disease. Invention provides preparing multifunctional hemopoietic proteins eliciting the enhanced activity with respect to stimulation of hemopoietic cells and eliciting the improved physical indices. Invention can be used for preparing chimeric multifunctional hemopoietic proteins.
EFFECT: improved preparing and producing method, valuable medicinal properties of protein.
22 cl, 19 dwg, 18 tbl, 117 ex
FIELD: organic synthesis.
SUBSTANCE: invention provides substituted 7-acylaminocephalosporins of formula I:
(I), where W denotes CH or B; V denotes NO; R1 hydrogen or С1-С4-alkyl; R3 hydrogen or ester residue; and R2 one of the following groups: , , , , in which X, R5, R6, R'6, R7, and Hal have meanings indicated in claims, in free state, in the form of salts and/or solvates, or, if such forms are stable, in the form of internal salt, quaternary salt, or their hydrates, possessing antimicrobial activity. Invention also discloses a method for preparing such compounds and a pharmaceutical connected containing them.
EFFECT: increased choice of antimicrobial preparations.
13 cl, 10 tbl, 225 ex
FIELD: medicine; medical engineering.
SUBSTANCE: means is composed of spherical and close-to-spherical 500-3000 mcm large microgranules. Microgranule matrix has at least one cross-linked polymer and fillers. The cross-linked polymer is taken as sodium alginate, or gelatin, or pectin, or carraginan, or agar-agar, or sodium salt of carboxycellulose, or copolymer of acrylic acid and butylacrylate, or their mixtures. The fillers are hyperosmolar, antiseptic, anesthetic and, when required, antioxidant compounds. Method involves placing microgranules into pyoinflammatory lesion focus through postoperative or fresh wound. Wound cavity space is filled with microgranules to not more than one-half of its volume. Then the wound is drained and covered with antiseptic bandage. The granules and bandage are changed once a day during 2-3 days.
EFFECT: enhanced effectiveness of treatment; prolonged drug concentration support in wound.
6 cl,1 tbl
SUBSTANCE: composition is constituted by effective amount of thymol obtained from plant Trychyspermum ammi, mint oil combination of mint oil containing required amounts of monoterpenes and isolated from Mentha spicata and Mentha arvensis, and typical additives. Invention also relates to preparation of the composition by mixing above ingredients and to method of treating patients by administering therapeutically effective amount of the composition.
EFFECT: created therapeutic agent overcoming drug resistance of bacteria and minimized or even eliminated secondary adverse effect of drug.
19 cl, 12 tbl, 11 ex
where R and R1have the meanings indicated in the claims
where the values of A, B, K, T, W, X, Y, U, V, Z, R1specified in paragraph 1 of the claims
< / BR>where Z represents (CH2)n, O or S; n is 0, 1 or 2; X represents 1-3 substituent, independently selected from hydrogen, halogen, (C1-6)alkyloxy,(C3-6)cycloalkane, (C6-12)aryloxy, (C6-12)aryl, teinila, CN, СООR6and (C1-4)alkyl, optionally substituted with halogen, or 2 substituent in adjacent positions together represent a condensed (C5-6)aryl group, or O-(CH2)m-O, where m is 1 or 2; Y is 1-3 selected from hydrogen, halogen, (C1-4)alkyloxy and (C1-4)alkyl, optionally substituted with halogen; R1represents COOR7; R2and R6are (C1-4)alkyl; R3, R4and R5independently represent hydrogen; R7, R8and R9independently represent hydrogen or (C1-4)alkyl; or pharmaceutically acceptable salts, and pharmaceutical compositions on their basis, with effect on the Central nervous system