thiourea and Bacterial-Infections

We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure-activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds.

Topics: Anti-Bacterial Agents; Bacterial Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Quinolines; Structure-Activity Relationship; Thiourea; Vancomycin

The reaction of lauroyl isothiocyanate and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was used to synthesize the title compound 2. Compound 2 could serve as the main building block in the synthesis of many target heterocyclic systems. Various fused pyrimidines were synthesized in the reactions of compound 2 with sodium ethoxide, hydrazine hydrate, phenyl hydrazine, ethyl carbazate, thiourea, and/or 2-aminothiophenol. The structures of the synthesized compounds were confirmed by microanalytical and spectral data.

Topics: Anti-Infective Agents; Bacteria; Bacterial Infections; Fungi; Humans; Isothiocyanates; Mycoses; Pyrimidines; Thiazines; Thiophenes; Thiourea

The aim of this study was to establish the antimicrobial activities of S-(3,4-dichlorobenzyl)isothiourea hydrochloride (A22) and a series of structurally related compounds against multidrug-resistant (MDR) bacteria. The minimum inhibitory concentrations (MICs) of 21 compounds were determined against 18 strains of pathogenic bacteria in addition to Pseudomonas aeruginosa (n=19) and Burkholderia cepacia complex (BCC) (n=20) isolated from the sputa of cystic fibrosis patients. Selected compounds were tested against further isolates, including P. aeruginosa (n=100), BCC (n=12) and Stenotrophomonas maltophilia (n=19). The interaction of S-(4-chlorobenzyl)isothiourea hydrochloride (C2) in combination with conventional antimicrobials was examined against 10 P. aeruginosa strains. Selected compounds were also tested against Enterobacteriaceae producing NDM-1 carbapenemase (n=64) and meticillin-resistant Staphylococcus aureus (MRSA) (n=37). Of the 21 compounds, 14 showed antimicrobial activity that was generally more pronounced against Gram-negative bacteria. Against P. aeruginosa, the most active compound was C2 [MIC for 50% of the organisms (MIC(50))=32μg/mL]. This compound was also the most active against BCC, with all isolates inhibited by 64μg/mL. For all ten strains of P. aeruginosa subjected to combination testing with C2 and conventional antimicrobials, a bactericidal effect was achieved with at least one combination. C2 and A22 both showed strong activity [MIC for 90% of the organisms (MIC(90))=4μg/mL] against Enterobacteriaceae that produced NDM-1 carbapenemase. Finally, S-(4-chlorobenzyl)-N-(2,4-dichlorophenyl)isothiourea hydrochloride showed good activity (MIC(90)=8μg/mL) against MRSA. This work establishes the activity of isothiourea derivatives against a broad range of clinically important MDR bacteria.

Topics: Anti-Bacterial Agents; Bacterial Infections; Burkholderia cepacia complex; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Thiourea

A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N'-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N'-(β-cyanoethyl)-N'-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N'-(β-cyanoethyl)-N'-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3). Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Models, Molecular; Pneumococcal Infections; Streptococcus pneumoniae; Thiourea; Urea

The identification of human inflammatory cells that express inducible nitric oxide synthase and the clarification of the role of inducible nitric oxide synthase in human infectious or inflammatory processes have been elusive. In neutrophil-enriched fractions from urine, we demonstrate a 43-fold increase in nitric oxide synthase activity in patients with urinary tract infections compared with that in neutrophil-enriched fractions from noninfected controls. Partially purified inducible nitric oxide synthase is primarily membrane associated, calcium independent, and inhibited by arginine analogues with a rank order consistent with that of purified human inducible nitric oxide synthase. Molecular, biochemical, and immunocytochemical evidence unequivocally identifies inducible nitric oxide synthase as the major nitric oxide synthase isoform found in neutrophils isolated from urine during urinary tract infections. Elevated inducible nitric oxide synthase activity and elevated nitric oxide synthase protein measured in patients with urinary tract infections and treated with antibiotics does not decrease until 6-10 d of antibiotic treatment. The extended elevation of neutrophil inducible nitric oxide synthase during urinary tract infections may have both antimicrobial and proinflammatory functions.

Topics: Adult; Aged; Anti-Bacterial Agents; Arginine; Bacterial Infections; Blotting, Western; Canavanine; Cell Membrane; Citrulline; Female; Guanidines; Humans; Immunohistochemistry; Isoenzymes; Leukocyte Common Antigens; Male; Middle Aged; Neutrophils; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Ornithine; Polymerase Chain Reaction; RNA, Messenger; Sulfonamides; Thiourea; Trifluoperazine; Urinary Tract Infections

The susceptibility of 1,000 recent bacterial isolates to noxythiolin was determined by the disc susceptibility method. No Gram-positive strains were resistant to this method but 56 (5.6%) of Gram-negative strains gave zones of inhibition of 12 mm diameter or less. The minimum inhibitory concentration (MIC) of the latter were determined by the agar incorporation method. No strains had MIC values greater than 4096 mg/litre. Since concentrations of 50,000 mg/litre can be used for topical treatment, these organisms may be considered susceptible.

Topics: Bacteria; Bacterial Infections; Microbial Sensitivity Tests; Noxythiolin; Thiourea

A controlled mixed peritoneal infection was produced by inoculation of bacteria into the peritoneum and peritonitis was allowed to become established. A laparotomy was performed and peritoneal toilet with a variety of agents was carried out. Local povidone-iodine in the inflamed peritoneum proved to be not only of no benefit but, in fact, to be toxic. In the standard concentrations recommended it proved lethal. Noxythiolin 2.5 per cent also had no beneficial effect. There was a significant difference between the effect of povidone-iodine when instilled into an inflamed peritoneum and instillation into the intact peritoneal cavity. We would advise caution in the use of these antiseptics in any situation in which local defence mechanisms have been compromised as a result of established infection.

Topics: Animals; Bacterial Infections; Disease Models, Animal; Male; Noxythiolin; Peritonitis; Povidone; Povidone-Iodine; Rats; Rats, Inbred Strains; Thiourea

Topics: Abscess; Adolescent; Adult; Bacterial Infections; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Noxythiolin; Thiourea

Our previous studies led to the development of a drug, 10-undecen-1- pseudothiourea iodide (AHR-1911), with the characteristics of a broad spectrum of antibacterial-antimycotic action and anti-inflammatory properties in experimental lesions induced by burns, dextran, albumin, carrageenin and kaolin. Using different vehicles for topical use, these two types of therapeutic property were separated, yielding two pharmaceutical preparations with different indications. One is a 0,25% AHR-1911 preparation in a polyoxyethyleneglycol base, which in in vivo experiments has the antimicrobial efficacy of gentamycin ointment; the other, containing 10% AHR-1911 in a vanishing cream base with triethanolamine stearate, possesses the anti-inflammatory efficacy of the newer topical steroid preparations. The clinical data for this latter preparation agree with the experimental findings. Its activity in clinical conditions was found first by Di Prisco in dermatological cases and confirmed in contact dermatitis patients by Riobueno. Its usefulness in burns and contusions with excoriations, without a single instance of secondary infection was reported by Rojas Mratínez; its effectiveness in bursitis and tenosynovitis may extend its field of application beyond that of dermatology. Particularly impressive were the good results obtained in insect bites, due possibly to the antihistaminic effect of the drug acting synergistically with the anti-inflammatory one. In the experience of all the clinicians the preparation was very well tolerated.

Topics: Bacterial Infections; Burns; Drug Evaluation; Humans; Inflammation; Isothiuronium; Ointments; Thiourea

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Candida albicans; Candidiasis; Escherichia coli; Escherichia coli Infections; Mice; Neomycin; Nystatin; Penicillins; Polymyxins; Staphylococcal Infections; Streptomycin; Tetracycline; Thiourea; Undecylenic Acids

Topics: Animals; Aorta, Abdominal; Bacterial Infections; Constriction; Hypoxia; Lung; Macrophages; Male; Mice; Phagocytosis; Phosphorus Radioisotopes; Pneumonia; Pulmonary Alveoli; Pulmonary Edema; Rats; Staphylococcal Infections; Thiourea