Effects of a thiosemicarbazide camphene derivative on Trichophyton mentagrophytes.
Thiosemicarbazides are compounds known for their biological activity, particularly their antimicrobial properties, which include activity against fungi. The difficulty of treating fungal diseases induced us to assess the antifungal properties of some novel thiosemicarbazide compounds. We selected the natural products limonene and camphene as sources for the preparation of these new thiosemicarbazide derivatives. The compound N(4)-[2,2-dimethyl-3-methylnorbornane]-thiosemicarbazide (TIO C) showed an antifungal effect on Trichophyton mentagrophytes, with values of MIC = 55 mmol L(-1) and MFC = 110 micromol L(-1). Scanning-electron microscopy showed a decrease in mycelium development and morphological alterations of T. mentagrophytes cultured on nail fragments and treated with TIO C. In an attempt to discover its mode of action, we noted that ergosterol is apparently not a target of TIO C activity. An effect of TIO C on T. mentagrophytes cell walls and dividing cross-walls was shown by observed impairment of the fluorescence of tissues stained with calcofluor white, a specific marker for fungal chitin, suggesting that the compound can affect and damage the cell-wall structure or may interfere with its formation, during cell division, growth, and morphogenesis. This approach to the synthesis of new derivatives might provide interesting compounds with greater biological activity in pharmacological research.
Yamaguchi
Mirian Ueda
MU
Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Brazil. mirianuy@irapida.com.br
Barbosa da Silva
Ana Paula
AP
Ueda-Nakamura
Tânia
T
Dias Filho
Benedito Prado
BP
Conceição da Silva
Cleuza
C
Nakamura
Celso Vataru
CV
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000081008:Bicyclic Monoterpenes; D002473:Cell Wall / Q000187:drug effects / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004875:Ergosterol / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009262:Nails / Q000382:microbiology / Q000648:ultrastructure; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D014249:Trichophyton / Q000166:cytology / Q000187:drug effects*
D000935:Antifungal Agents; D000081008:Bicyclic Monoterpenes; D004791:Enzyme Inhibitors; D012663:Semicarbazides; D013729:Terpenes; C005151:thiosemicarbazide; D000666:Amphotericin B; C019286:camphene; D004875:Ergosterol