nnd-502 and latoconazole

Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open-source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents.. Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole.. Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008-2 µg/ml, 0.001-0.064 µg/ml and 0.001-0.064 µg/ml, respectively. Even Ma. fahalii and Me. romeroi, which are not inhibited in growth by itraconazole at a concentration of 4 µg/ml, were inhibited by these azoles.. The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma.

Topics: Antifungal Agents; Humans; Imidazoles; Itraconazole; Madurella; Mycetoma; Thiazoles; Triazoles

In vitro antifungal activity of luliconazole against nondermatophytic moulds causing superficial infections was compared with that of five classes of 12 topical and systemic drugs. The minimum inhibitory concentration (MIC) of the drugs against the genera of Neoscytalidium, Fusarium, Aspergillus, Scedosporium, and Alternaria was measured via modified microdilution method. In results, the nondermatophytic moulds were found to be less susceptible to drugs to which Neoscytalidium spp. and Fusarium spp. were typically drug resistant. However, luliconazole was effective against all the genera tested, including afore-mentioned two species, and had the lowest MICs among the drugs tested.

Topics: Amphotericin B; Antifungal Agents; Clotrimazole; Fluconazole; Fungi; Humans; Imidazoles; Itraconazole; Ketoconazole; Miconazole; Microbial Sensitivity Tests; Morpholines; Sequence Analysis, DNA; Terbinafine; Triazoles; Voriconazole

Dermatophytes are a group of keratinophilic fungi that invade and infect the keratinized tissues and cause dermatophytosis. We investigated effectiveness of novel triazole (luliconazole and lanaconazole) in comparison with available antifungal agents against dermatophyte species isolated from patients with tinea pedis.. A total of 60 dermatophytes species were isolated from the patients with tinea pedis. Identification of species was done by DNA sequencing of the ITS1-5.8S rDNA-ITS2 rDNA region. In vitro antifungal susceptibility testing with luliconazole and lanaconazole and available antifungal agent was done in accordance with the Clinical and Laboratory Standards Institute, M38-A2 document.. In all investigated isolates, luliconazole had the lowest minimum inhibitory concentration (MIC) (MIC range=0.0005-0.004μg/mL), while fluconazole (MIC range=0.4-64μg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008μg/mL), followed by lanoconazole (0.003μg/mL), terbinafine (0.019μg/mL), itraconazole (0.085 μg/mL), ketoconazole (0.089μg/mL), econazole (0.097μg/mL), griseofulvin (0.351 μg/mL), voriconazole (0.583μg/mL) and fluconazole (11.58μg/mL).. The novel triazoles showed potent activity against dermatophytes and promising candidates for the treatment of tinea pedis caused by Trichophyton and Epidermophyton species. However, further studies are warranted to determine the clinical implications of these investigations.

Topics: Antifungal Agents; Arthrodermataceae; Dermatomycoses; Fluconazole; Griseofulvin; Humans; Imidazoles; Itraconazole; Ketoconazole; Microbial Sensitivity Tests; Terbinafine; Tinea; Tinea Pedis; Triazoles; Trichophyton; Voriconazole

The incidence of Aspergillus infections has recently increased remarkably in certain tropical and sub-tropical countries, with Aspergillus flavus being identified as the leading cause of infections after A. fumigatus. Lanoconazole (LAN) and luliconazole (LUL) are currently approved for topical treatment of cutaneous fungal infections. We aimed the in-vitro antifungal susceptibility testing of two imidazole, LAN and LUL against A. flavus.. One hundred and eighty-seven clinical and environmental A. flavus were tested originating from different climate zones of Iran between 2008 and 2015. The identification of all isolates was confirmed by using PCR-sequencing of β-tubuline ribosomal DNA gene. In-vitro antifungal susceptibility test was performed using CLSI guidelines against LAN, LUL, itraconazole (ITC), voriconazole (VRC), posaconazole (POS), Isavuconazole (ISA), amphotericin B (AMB), 5-flucytosine (5FC), caspofungin (CAS) and anidulafungin (AFG). The minimum inhibitory concentration (MIC) and minimum effect concentration (MEC) values were evaluated according to CLSI M38-A2 guidelines.. The geometric mean MICs for tested antifungals, in increasing order, were: 0.009 μg/mL for LUL (ranging from 0.004 to 0.062), 0.02 μg/mL for LAN (ranging from 0.004 to 0.125), POS (0.10), ISA (0.16), ITC (0.24), VRC (0.27), AMB (1.8) and 5FC (63.06) μg/mL. The mean value of MECs for AFG and CAS were 0.06 and 0.07, respectively.. Overall, LUL and LAN showed the lowest MIC against all isolates of A. flavus. Further studies are required to evaluate the in-vivo efficacy of these agents, and the possibility of using these agents in systemic infections.

Topics: Antifungal Agents; Aspergillus flavus; Humans; Imidazoles; Invasive Pulmonary Aspergillosis; Iran; Microbial Sensitivity Tests

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Topics: Adult; Antifungal Agents; Ascomycota; Child, Preschool; Drug Resistance, Fungal; Female; Humans; Imidazoles; Male; Microbial Sensitivity Tests; Middle Aged; Mycoses; Triazoles; Yeasts; Young Adult

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

In vitro susceptibilities of 100 clinical dermatophyte isolates belonging to five species from Iran toward lanoconazole and luliconazole were compared with ten other antifungal agents including econazole, itraconazole, miconazole, fluconazole, griseofulvin, butenafine, terbinafine, caspofungin, anidulafungin and tolnaftate. MIC and MEC values were analyzed according to CLSI M38-A2 document. The isolates were previously identified to the species level using PCR-RFLP on ITS rDNA region. The range of luliconazole and lanoconazole minimum inhibitory concentrations (MICs) was 0.016-0.032 and 0.063-1 μg/ml, respectively for dermatophyte species. Luliconazole and lanoconazole revealed potent activity against all dermatophyte isolates. Anidulafungin, caspofungin, and luliconazole showed the best activity with the lowest geometric mean 0.01, 0.016, and 0.018 μg/ml, respectively, followed by tolnaftate (0.06 μg/ml), terbinafine (0.07 μg/ml), itraconazole (0.183 μg/ml), butenafine (0.188 μg/ml), econazole (0.20 μg/ml), lanoconazole (0.24 μg/ml), griseofulvin (1.28 μg/ml), miconazole (2.34 μg/ml) and fluconazole (15.34 μg/ml). The current study demonstrated luliconazole and lanoconazole displayed excellent activity against all dermatophyte isolates, although the majority of dermatophyte isolates showed low susceptibility to griseofulvin and very low to miconazole, and fluconazole.

Topics: Antifungal Agents; Arthrodermataceae; Dermatomycoses; DNA, Ribosomal Spacer; Humans; Imidazoles; Iran; Microbial Sensitivity Tests; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length

Topics: Antifungal Agents; Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Humans; Imidazoles; Microbial Sensitivity Tests

The in vivo efficacy of terbinafine was compared to lanoconazole and luliconazole in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Topical antifungal treatment commenced three days post-infection, and each agent was applied once daily for seven consecutive days. Upon completion of the treatment period, evaluations of clinical and mycological efficacies were performed, as was scanning electron microscopy (SEM) analyses. Data showed that while all tested antifungals demonstrated significant mycological efficacy in terms of eradicating the fungi over untreated control, terbinafine and luliconazole showed superior clinical efficacy compared to lanoconazole (P-values < 0.001 & 0.003, respectively). Terbinafine demonstrated the highest clinical percent efficacy. SEM analysis revealed hairs from terbinafine and lanoconazole-treated animals had near complete clearance of fungi, while samples from luliconazole-treated animals were covered with debris and few conidia. This study demonstrates that, in general, terbinafine possessed similar efficacy to lanoconazole and luliconazole in the treatment of dermatophytosis. Terbinafine tended to have superior clinical efficacy compared to the azoles tested, although this difference was not statistically significant against luliconazole. This apparent superiority may be due to the fungicidal activity of terbinafine compared to the fungistatic effect of the other two drugs.

Topics: Administration, Topical; Animals; Antifungal Agents; Dermatomycoses; Disease Models, Animal; Guinea Pigs; Imidazoles; Male; Naphthalenes; Terbinafine; Treatment Outcome; Trichophyton

The in vitro activity of NND-502, a novel antifungal imidazole compound, was tested against the three major Malassezia species by an agar dilution method with modified Dixon medium and compared with the activities of three reference antifungal drugs of topical use, lanoconazole (LCZ), bifonazole (BFZ) and terbinafine (TBF). The geometric mean (GM)-MICs of NND-502 for 25 strains of M. furfur, 15 strains of M. sympodialis and ten strains of M. slooffiae were approximately 1.4, 0.1 and 1.0 mg/l, respectively, showing the greatest activity against M. sympodialis and the least against M. slooffiae. These values were similar to that of LCZ, but four to 69 times lower than that of BFZ and two to three times lower than that of TBF. The results suggest that NND-502 might be beneficial in the treatment of Malassezia-associated skin diseases.

Topics: Antifungal Agents; Dermatomycoses; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Heterocyclic Compounds; Humans; Imidazoles; In Vitro Techniques; Malassezia; Microbial Sensitivity Tests; Naphthalenes; Species Specificity; Terbinafine; Tinea Versicolor