Haloprogin

By screening a drug library comprising FDA approved compounds, we discovered a potent interaction between the antifungal agent haloprogin and the experimental organometallic drug RAPTA-T, to synergistically induce cancer cell killing. The combination of these two small molecules, even at low doses, elicited an improved therapeutic response on tumor growth over either agent alone or the current treatment used in the clinic in the highly aggressive syngeneic B16F10 melanoma tumor model, where classical cytotoxic chemotherapeutic agents show little efficacy. The combination with the repurposed chemodrug haloprogin provides the basis for a new powerful treatment option for cutaneous melanoma. Importantly, because synergistic induction of tumor cell death is achieved with low individual drug doses, and cellular targets for RAPTA-T are different from those of classical chemotherapeutic drugs, a therapeutic strategy based on this approach could avoid toxicities and potentially resistance mechanisms, and could even inhibit metastatic progression.

The synthesis and microbiological activity of a new series of 5(or 6)-methyl-2-substituted benzoxazoles (IVa-n) and benzimidazoles (Va-h) were described. The in vitro microbiological activity of the compounds was determined against gram-positive, gram-negative bacteria and the yeast Candida albicans in comparison to reference drugs. Microbiological results indicated that the derivatives possessed a broad spectrum of activity against the tested microorganisms and the compounds IVa-g, IVi-k, IVn, Vb-c and Vh showed significant activity against Pseudomonas aeruginosa having MIC values of 25 micrograms/ml, providing higher potencies than the reference drugs tetracycline and streptomycin. Moreover, the derivative 5-methyl-2-(p-chlorobenzyl)benzoazole (IVb) possessed the same potency against Candida albicans as the reference drugs oxiconazole and haloprogin having a MIC value of 6.25 mg/ml. However, none of the derivatives showed a better spectrum of activity than the reference drugs.