Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization.
نویسندگان
چکیده
Tamoxifen (TAM), an estrogen receptor antagonist used primarily to treat breast cancer, has well-recognized antifungal properties, but the activity of TAM has not been fully characterized using standardized (i.e., CLSI) in vitro susceptibility testing, nor has it been demonstrated in an in vivo model of fungal infection. In addition, its mechanism of action remains to be clearly defined at the molecular level. Here, we report that TAM displays in vitro activity (MIC, 8 to 64 microg/ml) against pathogenic yeasts (Candida albicans, other Candida spp., and Cryptococcus neoformans). In vivo, 200 mg/kg of body weight per day TAM reduced kidney fungal burden (-1.5 log(10) CFU per g tissue; P = 0.008) in a murine model of disseminated candidiasis. TAM is a known inhibitor of mammalian calmodulin, and TAM-treated yeast show phenotypes consistent with decreased calmodulin function, including lysis, decreased new bud formation, disrupted actin polarization, and decreased germ tube formation. The overexpression of calmodulin suppresses TAM toxicity, hypofunctional calmodulin mutants are hypersensitive to TAM, and TAM interferes with the interaction between Myo2p and calmodulin, suggesting that TAM targets calmodulin as part of its mechanism of action. Taken together, these experiments indicate that the further study of compounds related to TAM as antifungal agents is warranted.
منابع مشابه
In vitro and in vivo antifungal activity of Allium hirtifolium and Allium sativum
Objective: One of the major clinical problems is the resistance of Candida speciestowards most of antifungals. The search for new antifungal drug from plants have helped to overcome this problem. This study evaluated the effects of Allium hirtifolium and Allium sativumextracts on Candida tropicalis both in vitro and in a mouse model of systemic candidiasis. Materials and Methods: In this study,...
متن کاملSynthesis, Spectral Characterization, In-vitro Antibacterial and Antifungal Activities of Novel (2e)-Ethyl-2-(2-(2, 4-Dinitrophenyl) Hydrazono)-4-(Naphthalen-2-yl)-6-Arylcyclohex-3-Enecarboxylates
In a search for new leads towards potent antimicrobial agents, an array of novel (2E)-ethyl-2-(2-(2,4-dinitrophenyl)hydrazono)-4-(naphthalen-2-yl)-6-arylcyclohex-3-ene carboxylates 17-24 were synthesized and characterized through their melting point, elemental analysis, MS, FT-IR, one-dimensional NMR (1H, D2O exchanged 1H and 13C), two dimensional HOMOCOR and HSQC spectroscopic data. In-vitro m...
متن کاملSynthesis, Spectral Characterization, In-vitro Antibacterial and Antifungal Activities of Novel (2e)-Ethyl-2-(2-(2, 4-Dinitrophenyl) Hydrazono)-4-(Naphthalen-2-yl)-6-Arylcyclohex-3-Enecarboxylates
In a search for new leads towards potent antimicrobial agents, an array of novel (2E)-ethyl-2-(2-(2,4-dinitrophenyl)hydrazono)-4-(naphthalen-2-yl)-6-arylcyclohex-3-ene carboxylates 17-24 were synthesized and characterized through their melting point, elemental analysis, MS, FT-IR, one-dimensional NMR (1H, D2O exchanged 1H and 13C), two dimensional HOMOCOR and HSQC spectroscopic data. In-vitro m...
متن کاملAntifungal potential of tolnaftate against Candida albicans in the treatment of onychomycosis: development of nail lacquer and ex vivo characterization
Onychomycosis constitutes the most common fungal infection of nail affecting finger and toe nails as well. Antifungals found to be effective in the treatment of onychomycosis. However, transport of oral antifungal agents exhibits more toxicity and requires longer treatment period. Medicated nail lacquers proved to cause lesser toxicity and required shorter treatment period. It provides not only...
متن کاملNew Benzimidazoles Derivatives: Synthesis, Characterization and Antifungal Activities
One of the most important goals in medicinal chemistry is the development of new heterocyclic compounds with pharmaceutical activity. Thus, a novel series of the derivatives of benzimidazole were synthesized and the structures of all the synthesized compounds have been confirmed by IR, 1 H- and 13C-NMR, Mass Spectroscopy and elemental analysis. The title compounds have been evaluated for antifu...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 53 8 شماره
صفحات -
تاریخ انتشار 2009