Interaction between ketoconazole, amphotericin B and terbinafin and three diazenumdiolates in concomitant uses against some fugal species

A checkerboard broth microdilution method was performed to investigate the in vitro antifungal activities of three diazeniumdiolates derivatives (DETA/NO, DPTA/NO, DEA/NO) alone and in combination with ketoconazole, amphotricin B or terbinafine against five Candida species, Cryptococcus neoformance and four dermatophyte strains. MICs and MLCs were recorded, and synergy was calculated by using fractional inhibitory and fractional lethal concentration index. DETA/NO with a half-life of 57h at 25°C showed antifungal activity against all tested dermatophyte species (MIC 0.150 to 2.5mg/ml), DPTA/NO with a half life of 3h at 37°C showed antifungal activity against five species of Candida and Cryptococcus neoformans, and DEA/NO with a half life of 2 min at 37°C and 16 min at 25° C did not show antifungal activity against tested strains. Combinations of DPTA-NO with either ketoconazole or amphotericin B were either synergistic or indifferent for all tested strain of Candida and Cryptococcus neoformance. DETA/NO was unable to enhance the antifungal activity of terbinafine against dermatophyte strains. Even where no synergistic activity was achieved, there was still a decrease in the MIC of one or both drugs which were used in combination. Antagonism was observed between terbinafine and DETA-NO against Trichophyton rubrum. Our result suggests that DETA/NO and DPTA/NO may be useful for development of new therapeutic strategies for treatment of dermatophyte and Candida infections. Clinical studies are warranted to elucidate the potential utility of these combination therapies

Xanthomicrol is the main cytotoxic component of Dracocephalum kotschyii and a potential anti-cancer agent

Spinal-Z, a methanolic mixture of dried powdered seeds of Peganum harmala Linn. and leaf of Dracocephalum kotschyii Boiss. is an Iranian ethno-medical remedy. It has been used for the treatment of various types of cancer for many years. To evaluate the use of Spinal-Z in treatment of cancer, we examined its effects against a panel of malignant cell lines and tumors induced in mice. The in vitro antiproliferative activities of Spinal-Z, the seed extract of P. harmala and the leaf extract of D. kotschyii were determined using the MTT assay. The concentration of the agent required to inhibit cell growth by 50 (IC50) was estimated. In addition, the anti-tumor activities of the remedy and its constituents were investigated. Viability of cells treated with Spinal-Z and its components decreased in a dose dependent manner. Spinal-Z and its components showed cytotoxic effects against all cell lines tested. The leaf extract of D. kotschyii showed a greater preferential cytotoxic effect than the seed extract of P. harmala and Spinal-Z, on all cell lines tested. Harmine showed cytotoxicity against HL60 and K562 cell lines. This could explain the cytotoxic effect of P. harmala on these cells. The leaf extract of D. kotschyii was able to inhibit tumor proliferation in mice. The active ingredient in the leaf extract of D. kotschyii appears to be a flavone identified as xanthomicrol. Xanthomicrol was able to inhibit proliferation of a number of malignant cells. The cytotoxic effects of xanthomicrol were more selective towards malignant cells than doxorubicin. © 2005 Elsevier Ltd. All rights reserved