nnd-502 and liranaftate

The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of luliconazole against Trichophyton rubrum (14 strains) and Trichophyton mentagrophytes (14 strains), which are the most common cause of tinea, were compared with those of 6 topical antifungal drugs of lanoconazole, bifonazole, efinaconazole, liranaftate, naftifine and terbinafine.　Luliconazole showed the most potent antifungal activity (MIC90 =0.00098 μg/ml and MFC90 =0.0078 μg/ml) among the compounds tested against the two species. Efinaconazole and bifonazole, the drug of azole-class, showed a large MFC/MIC ratio. On the other hand, these ratios of luliconazole and lanoconazole were as small as those of liranaftate, naftifine and terbinafine which are thought to possess fungicidal mechanism. These results suggest that luliconazole possesses fungicidal activity against both species of Trichophyton.　In this study, we found that luliconazole had the most potent antifungal activity among the major topical antimycotics used in Japan and the US. Luliconazole would be the best-in-class drug for dermatophytosis in clinics.

Topics: Allylamine; Antifungal Agents; Drug Resistance, Fungal; Imidazoles; Microbial Sensitivity Tests; Naphthalenes; Pyridines; Terbinafine; Thiocarbamates; Triazoles; Trichophyton

The fungicidal activities of the thiocarbamate antifungal agent liranaftate were compared to those of luliconazole, amorolfine hydrochloride and ketoconazole against twelve stock strains of three species of dermatophytes. The MICs of 0.001-0.009 microg/ml of luliconazole against Trichophyton rubrum (n=6)were the lowest among the agents tested, but its MCCs were considerably higher. Consequently, the antifungal potency of luliconazole was considered fungistatic. In contrast to this, the MCCs of 0.009-0.039 microg/ml of liranaftate against T. rubrum were the lowest and similar to its MICs. These results showed that liranaftate was fungicidal. All antifungals except ketoconazole tended to be fungicidal against both T. mentagrophytes (n=3)and Microsporum gypseum (n=3). In time-kill studies, liranaftate showed the greatest decrease to a below detection limit in viable counts of T. rubrum. The degree of killing of the strain by amorolfine was not greater than that seen by liranaftate, and little reduction of the viable counts by luliconazole and ketoconazole was observed irrespective of concentrations of the agents. Conversely, there were no differences among four agents in fungicidal activities against T.mentagrophytes. The killing activities of liranaftate against M. gypseum were also higher than those of comparable agents, as true of T. rubrum described above. In this study we found that it was harder to kill T. rubrum than other dermatophytes. Therefore, liranaftate with its potent fungicidal activities was suggested an efficacious agent for the treatment of dermatophytes.

Topics: Antifungal Agents; Arthrodermataceae; Imidazoles; Ketoconazole; Morpholines; Naphthalenes; Pyridines; Thiocarbamates; Trichophyton