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 of a new series of 5-or 6-methyl-2-(2,4-disubstituted phenyl) benzoxazoles (4, 5) is described in order to determine their antimicrobial activities and feasible structure-activity relationships. The synthesized compounds were tested in vitro against three Gram-positive bacteria, three Gram-negative bacteria and the yeast Candida albicans, in comparison with several control drugs. Microbiological results exhibited that the synthesized compounds possess a broad spectrum of antibacterial activity against the tested microorganisms. The compounds 4b and 4c indicated some antibacterial activity against Staphylococcus aureus having a minimum inhibitory concentration (MIC) of 12.5 micrograms/ml. Moreover, the compound 5a revealed a significant antibacterial activity against the enterobacter Pseudomonas aeruginosa showing a MIC value of 25 micrograms/ml, i.e. more potent than the control drugs tetracycline and streptomycin. For the antimycotic activity against the yeast C. albicans, the derivative 4c was found to be more active than the other synthesized compounds with a MIC value of 12.5 micrograms/ml, but one-fold less potent than the control drugs oxiconazole and haloprogin.