RESUMO
Lack of novel antifungal agents and severe drug resistance has led to high incidence and associated mortality of invasive fungal infections. To tackle the challenges, novel antifungal agents with anti-resistant potency are highly desirable. Thus, derivatives of curcumin were synthesized to restore the effectiveness of fluconazole (FLC) against FLC-resistant Candida spp. and structure-activity relationships were then discussed. Some novel derivatives showed promising features as novel antifungal lead compounds. Of them, compound 4 showed good alone or synergistic antifungal activity against FLC-resistant Candida spp. Moreover, compound 4 was proven as a potent inhibitor of Candida albicans biofilm formation and yeast-to-hypha morphological transition whether used alone or in combination with FLC, which was further confirmed by the inhibitory effect on cellular surface hydrophobicity of C. albicans. Compound 4 also inhibits intracellular ATP production of C. albicans and disrupts membrane permeability of C. albicans when used in combination with FLC. The results highlighted the potential of curcumin derivatives to overcome fluconazole-related and biofilm-related drug resistance.
Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Curcumina/análogos & derivados , Fluconazol/farmacologia , Trifosfato de Adenosina/metabolismo , Antifúngicos/síntese química , Antifúngicos/química , Candida/efeitos dos fármacos , Candida/metabolismo , Candida/fisiologia , Linhagem Celular , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
Novel coaxial heterojunction carbon nanofibers, fabricated by electro-spinning a mixture of hydro-pitch and polyacrylonitrile, served as the counter electrode for dye-sensitized solar cells. Their high power conversion efficiency, being comparable to that of Pt CE, was achieved due to their good conductivity and high heteroatom content.
RESUMO
Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 µg ml-1 fluconazole and 64 µg ml-1 or 128 µg ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis. The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.
RESUMO
To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Chalconas/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Chalconas/síntese química , Chalconas/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: Identification of the primary tumour can prolong the life expectancy of patients with primary unknown cervical lymph node metastasis (PUCLNM) through targeted therapy. This study investigated the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) at identifying primaries in patients with PUCLNM. METHODS: Twenty-seven patients (21 males and 6 females, median age 48.2 ± 16.3, age range 30-73) with PUCLNM underwent FDG PET-CT to search for the primary tumour, which could not be detected by conventional diagnostic modalities. The results were analysed and correlated with either pathological findings or clinical follow up. RESULTS: Pathological FDG uptake suspicious for the primary was detected in 13 cases, while the primary tumour remained occult in 14 cases. Eleven of 13 patients with suspected primaries were confirmed by histological findings. One with a coexisting second tumour and three with unexpected distant metastases were found in patients with confirmed primaries. The most common primary location in patients with PUCLNM found in our study was nasopharynx. In those 14 patients with negative FDG PET-CT results, only one patient had a primary malignancy that was proven histologically after endoscopy with biopsy during a period of clinical follow up. The sensitivity, specificity, accuracy and positive predictive values of FDG PET-CT were 91.7, 86.7, 88.9 and 84.6%, respectively. CONCLUSION: FDG PET-CT is a useful tool to help search for unknown primaries in patients with cervical lymph node metastasis and has an acceptable diagnostic yield for the detection of distant malignancies.