Effects of a Thiosemicarbazide Camphene Derivative on Trichophyton mentagrophytes.docVIP

Molecules 2009, 14, 1796-1807; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Effects of a Thiosemicarbazide Camphene Derivative on Trichophyton mentagrophytes Mirian Ueda Yamaguchi 1,*, Ana Paula Barbosa da Silva 2, Tania Ueda-Nakamura 1,3, Benedito Prado Dias Filho 1,3, Cleuza Concei??o da Silva 2 and Celso Vataru Nakamura 1,3,* 1 Programa de Pós-gradua??o em Ciências Farmacêuticas, Universidade Estadual de Maringá, PR, Brazil; E-mails: mirianuy@.br (M-U.Y.), tunakamura@uem.br (T-U.N.), bpdfilho@uem.br (B-D.F.), cvnakamura@uem.br (C-V.N.) 2 Departamento de Química, Universidade Estadual de Maringá, PR, Brazil; E-mails: silvaapb@.br (A-B.S.), ccsilva@uem.br (C-C.S.) * Author to whom correspondence should be addressed; E-mail: cvnakamura@uem.br; Tel: +55 44 3261 1397; Fax: +55 44 3261 4860. Received: 24 March 2009; in revised form: 6 May 2009 / Accepted: 7 May 2009 / Published: 13 May 2009 Abstract: 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 ?mol L-1 and MFC = 110 ?mol 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