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In vitro interaction of osthol (Ost) and fluconazole (FLC) was investigated against 11 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay. The results of agar diffusion test confirmed the synergistic interaction. We used an enteric material Eudragit S100 for preparation of Ost nanoparticle (Ost-NP) to improve the oral bioavailability, biological activity of Ost. The physicochemical characteristics of Ost-S100-NP revealed Ost-S100-NP with mean particle size of 55.4±0.4 nm, encapsulation efficiency of 98.95±0.06%, drug loading efficiency of 23.89±0.25%, yield of 98.5±0.1% and a polydispersity index (PDI) of 0.165. As the Ost concentration-time curve showed, Ost-S100-NP can increase the plasma concentration and relative bioavailability of Ost compared with Ost-suspension by oral administration. In vivo, Ost-S100-NP enhanced the therapeutic efficacy of Ost against FLC-resistant C. albicans in immunosuppressed candidiasis mice model. The available information strongly suggests that Ost-S100-NP may be used as a promising compound against drug-resistant fungi.

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the Rh I -catalyzed enantioselective addition reaction of arylboronic acids to N-diphenylphosphinyl (N-DPP)-protected aldimines. Unlike the analogous Rh I -catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N-DPP-aldimines and arylboronic acids, producing the desired optically active N-DPP-protected amines with yields between 31-99 % and with ee values up to 91-99 %. The synthetic utility of the method was demonstrated by the conversion of N-DPP-protected amine 3 ae into the antifungal agent, bifonazole (13)., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This study aimed to investigate the antifungal activity of Rubus chingii extract in combination with fluconazole (FLC) against FLC-resistant Candida albicans 100 in vitro. A R. chingii extract and FLC-resistant C. albicans fungus suspension were prepared. The minimum inhibitory concentration and fractional inhibitory concentration index of R. chingii extract combined with FLC against C. albicans were determined, after which growth curves for C. albicans treated with R. chingii extract, FLC alone and a combination of these preparations were constructed. Additionally, the mechanisms of drug combination against C. albicans were explored by flow cytometry, gas chromatographic mass spectrometry and drug efflux pump function detection. R. chingii extract combined with FLC showed significant synergy. Flow cytometry suggested that C. albicans cells mainly arrest in G1 and S phases when they have been treated with the drug combination. The drug combination resulted in a marked decrease in the ergosterol content of the cell membrane. Additionally, efflux of Rhodamine 6G decreased with increasing concentrations of R. chingii extract. R. chingii extract combined with FLC has antifungal activity against FLC-resistant C. albicans., (© 2016 The Societies and John Wiley & Sons Australia, Ltd.)

The objective of this study was to determine the effect of iontophoresis on the delivery of terbinafine hydrochloride (4%, w/w) into and across hairless rat skin. In vitro skin uptake and permeation studies were performed using Franz diffusion cells. Anodal iontophoresis was applied for 1h at current densities of 0.2, 0.3 and 0.4mA/cm(2). In addition, iontophoresis was applied for 15, 30, 45 and 60min. Studies were conducted in which the formulation was either removed or left in contact with the skin following iontophoresis and then passive delivery was assessed 23h later. Tape stripping and skin extraction were performed to quantify drug levels in the stratum corneum and the underlying skin, respectively. The samples were analyzed using HPLC. The amount of drug delivered into the stratum corneum following iontophoresis was not significantly different from the amount delivered passively (p>0.05). However, drug levels in the underlying skin were significantly higher for the iontophoretic group. The amount of terbinafine delivered into the skin layers was influenced by current density and duration of current application. Leaving the drug formulation in contact with the skin during the post-iontophoretic period had a significant effect on drug levels delivered into skin layers. Iontophoresis enhanced the delivery of terbinafine hydrochloride into the skin layers and, therefore, may be used to improve the treatment of skin fungal infections., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis. [ABSTRACT FROM AUTHOR]

Covering: up to the second quarter of 2020 Threat or treat? While pathogenic bacteria pose significant threats, they also represent a huge reservoir of potential pharmaceuticals to treat various diseases. The alarming antimicrobial resistance crisis and the dwindling clinical pipeline urgently call for the discovery and development of new antibiotics. Pathogenic bacteria have an enormous potential for natural products drug discovery, yet they remained untapped and understudied. Herein, we review the specialised metabolites isolated from entomopathogenic, phytopathogenic, and human pathogenic bacteria with antibacterial and antifungal activities, highlighting those currently in pre-clinical trials or with potential for drug development. Selected unusual biosynthetic pathways, the key roles they play (where known) in various ecological niches are described. We also provide an overview of the mode of action (molecular target), activity, and minimum inhibitory concentration (MIC) towards bacteria and fungi. The exploitation of pathogenic bacteria as a rich source of antimicrobials, combined with the recent advances in genomics and natural products research methodology, could pave the way for a new golden age of antibiotic discovery. This review should serve as a compendium to communities of medicinal chemists, organic chemists, natural product chemists, biochemists, clinical researchers, and many others interested in the subject. [ABSTRACT FROM AUTHOR]

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the RhI-catalyzed enantioselective addition reaction of arylboronic acids to N-diphenylphosphinyl ( N-DPP)-protected aldimines. Unlike the analogous RhI-catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N-DPP-aldimines and arylboronic acids, producing the desired optically active N-DPP-protected amines with yields between 31-99 % and with ee values up to 91-99 %. The synthetic utility of the method was demonstrated by the conversion of N-DPP-protected amine 3 ae into the antifungal agent, bifonazole ( 13). [ABSTRACT FROM AUTHOR]

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections. [ABSTRACT FROM AUTHOR]