amphotericin-b and imidazole

The increased use of immunosuppressive regimens in organ transplantation and in the treatment of malignant lesions and the epidemic of acquired immunodeficiency syndrome (AIDS) are major reasons for the greater prevalence of fungal infections seen in clinical practice during the past decade. The traditional cornerstone of antifungal treatment, amphotericin B, continues to play a major role in deep-seated mycotic infections. The indications for intravenously administered miconazole have become limited. Orally administered flucytosine remains useful in certain infections, particularly cryptococcal meningitis. The new orally administered antifungal agents ketoconazole and fluconazole have been approved for clinical use and have supplanted amphotericin B in certain situations. Investigational antifungal agents, including liposomal amphotericin B, itraconazole, and saperconazole, hold promise for the future. Active investigation in the development of new antifungal agents is expected to continue.

Topics: Amphotericin B; Antifungal Agents; Flucytosine; Humans; Imidazoles; Mycoses; Thromboxane-A Synthase; Triazoles

In this paper we report the SAR studies of a series of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)amide and N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)sulfonamide derivatives 6(a-o) and 7(a-o), were synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The preparation of the key intermediate highlights an optimized palladium catalyzed (Pd₂(dba)₃/RuPhos) Buchwald cross-coupling of intermediate 2 and 3. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7d, 7f, 7h and 7n displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Topics: Amides; Anti-Infective Agents; Antitubercular Agents; Bacteria; Bacterial Infections; Fungi; Humans; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycoses; Structure-Activity Relationship; Sulfonamides

Two different series of N-substituted imidazolium oximes and their monoquaternary salts were synthesized and biologically tested with respect to their ability to inhibit growth a diverse panel of antibiotic susceptible Gram-positive and antibiotic resistant Gram-negative bacteria as well fungal strains. The newly synthesized compounds were analyzed by spectral studies to confirm their structure. The preliminary results showed that all compounds tested possess promising antimicrobial potential against both susceptible Gram-positive and antibiotic resistant Gram-negative isolates, exhibiting a wide range of MIC values from 0.14 to 100.0 μg/mL. The structure-activity relationship demonstrates that the p-methylphenyl and p-fluorophenyl groups in monoquaternary salts 6 and 7 attached directly to the imidazolium ring could be essential for observed remarkable inhibitory profiles against clinically important pathogens Pseudomonas aeruginosa (MIC=0.14 μg/mL) and Klebsiella pneumoniae (MIC=1.56 μg/mL). Furthermore, the broth microdilution assay was then used to investigate the antiresistance efficacy of compound 7 against fourteen extended-spectrum β-lactamase (ESBL)-producing strains in comparison to eight clinically relevant antibiotics. Compound 7 exhibited a remarkable antiresistance profiles ranging between 0.39 and 12.50 μg/mL against all of ESBL-producing strains, which leads to the suggestion that may be interesting candidate for development of new antimicrobials to combat multidrug resistant Gram-negative bacteria.

Topics: Anti-Infective Agents; Bacterial Infections; Drug Resistance, Multiple; Fungi; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Imidazoles; Microbial Sensitivity Tests; Mycoses; Oximes

Imidazole/benzotriazole analogues substituted piperidin-4-one derivatives (17-26) have been synthesized. Their chemical structures were characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. In addition, single crystal X-ray diffraction has also been recorded for compounds 21 and 23. The synthesized compounds were subjected to their in vitro antibacterial and antifungal activities against pathogenic microbial strains. The results pointed out that compounds 19 & 24 against B. subtilis and 20 & 24 against E. coli were explored superior inhibition activity.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Crystallography, X-Ray; Fungi; Imidazoles; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Piperidines; Stereoisomerism; Triazoles

A series of new 3-[4-(1H-imidazol-1-yl) phenyl]prop-2-en-1-ones were synthesized by the condensation of various acetophenones with 4-(1H-imidazol-1-yl) benzaldehyde which was itself prepared by the N-arylation of imidazole using hexadecyltrimethylammonium bromide as catalyst for the first time. All the synthesized compounds were subjected to preliminary evaluation for their anti-leishmanial, anti-oxidant and anti-fungal activities. Few of the synthesized compounds showed significant activities.

Topics: Antifungal Agents; Antioxidants; Antiparasitic Agents; Chalcones; Crystallography, X-Ray; Fungi; Imidazoles; Leishmania; Leishmaniasis; Models, Molecular

1-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were synthesized and tested for their in vitro antifungal and antimycobacterial activities. These imidazole derivatives showed an excellent antifungal activity against a clinical strain of Candida albicans and an interesting antitubercular activity against Mycobacterium tuberculosis H(37)Rv reference strain.

Topics: Anti-Bacterial Agents; Antifungal Agents; Candida albicans; Hydrogen; Imidazoles; Magnetic Resonance Spectroscopy; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Structure-Activity Relationship

To report a case of fungal keratitis of the eye caused by Pichia anomala in a patient with systemic lupus erythematous and Stevens-Johnson syndrome.. This was a retrospective chart review.. A 50-year-old woman with systemic lupus erythematosus presented with ocular pain of 4-day duration. Culture of corneal scrapings was positive for P. anomala. Clinically, the organism appeared to respond to topical natamycin, amphotericine B, and oral itraconazole.. A rare case of P. anomala-associated keratitis was successfully treated with topical amphotericin B, natamycin, and systemic inidazole.

Topics: Amphotericin B; Antifungal Agents; Corneal Ulcer; Drug Therapy, Combination; Eye Infections, Fungal; Female; Humans; Imidazoles; Lupus Erythematosus, Systemic; Middle Aged; Mycoses; Natamycin; Pichia; Stevens-Johnson Syndrome

The main antifungal agents used for deep-seated mycotic infections are the broad-spectrum antifungal drug amphotericin B, the narrow-spectrum agent flucytosine, and the newer broad-spectrum agents ketoconazole, miconazole, and itraconazole. Amphotericin B remains the cornerstone of antifungal therapy. For the treatment of cryptococcal meningitis, the current recommendation is for the combined use of amphotericin B and flucytosine. Published clinical experience with the newer agents is limited. Not all patients from whom fungal agents have been isolated require treatment; the extent of the fungal infection should be determined, when possible, for evaluation of the need for treatment.

Topics: Amphotericin B; Antifungal Agents; Flucytosine; Humans; Imidazoles; Mycoses; Triazoles

Copiamycin, a macrocyclic lactone antifungal antibiotic, was found to potentiate the antifungal effect of imidazole compounds, ketoconazole in particular. The potentiation of two nominally fungistatic agents in vitro was substantiated by a marked reduction of the minimum inhibitory and minimum fungicidal concentrations when the drugs were used in combination. The effectiveness of this synergistic combination was also demonstrated in experimental murine candidosis. Evidence is presented to suggest that this combined effect is due, at least in part, to the ionophoretic property of copiamycin. Whereas amphotericin B induces a marked increase in cellular permeability, this antibiotic does not possess the ionophoretic action of copiamycin, indicating that the enhancement of copiamycin activity and significant reduction of amphotericin B activity by ketoconazole pretreatment can be ascribed not only to changes in membrane permeability of the test organisms, but also to the different action mechanisms of copiamycin and amphotericin B. It is thus plausible that the strong synergism of copiamycin with imidazole compounds is related to the ionophoretic activity of the antibiotic. Further studies on the biochemical mechanism of this synergistic effect are being conducted together with an assessment of the clinical significance of this drug combination.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Clotrimazole; Drug Synergism; Fungi; Imidazoles; Ketoconazole; Lactones; Mitochondrial Swelling

The chemotherapy of systemic fungal infections remains problematic due to a lack of alternative agents. There are only 3 drugs available: Amphotericin B, 5-Fluorcytosine and the new iv.-formulation of Miconazole. There are as yet limited experiences concerning one of the Imidazole-derivatives of the new generation, Ketoconazole. The main antimycotic and pharmacokinetic properties of these drugs will be discussed.

Topics: Amphotericin B; Antifungal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Flucytosine; Humans; Imidazoles; Miconazole; Mycoses