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JAC Advance Access published online on November 28, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg019
© 2002 by The British Society for Antimicrobial Chemotherapy
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© 2002 The British Society for Antimicrobial Chemotherapy

Original Paper

In vitro and in vivo anticryptococcal activities of a new pyrazolo-isothiazole derivative

Francesco Barchiesi 1*, Maria E. Milici 2, Daniela Arzeni 1, Anna M. Schimizzi 1, Giuseppe Pizzo 3, Giovanni M. Giammanco 2, Daniele Giannini 4, Maurizio Manfrini 5, Giorgio Scalise 1, Chiara B. Vicentini 5

1 Istituto di Malattie Infettive e Medicina Pubblica, Università degli Studi di Ancona, Azienda Ospedaliera Umberto I°, Via Conca 60020, Torrette di Ancona, Ancona
2 Dipartimento di Igiene e Microbiologia, Università di Palermo, Palermo
3 Dipartimento di Discipline Odontostomatologiche, Università di Palermo, Palermo
4 Centro di Gestione Presidenza Medicina e Chirurgia, Università di Ancona, Ancona
5 Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Ferrara, Italy

* Corresponding author. E-mail: cmalinf{at}popcsi.unian.it.

Received 2 January 2002 ; revised 4 June 2002 ; accepted 27 September 2002

Abstract

We investigated the activity of a pyrazolo-isothiazole derivative (G8) against Cryptococcus neoformans. A first screening test showed that G8 at 10 mg/L inhibited the growth of 14 of 15 clinical isolates tested. Killing experiments showed that fungicidal activity was achieved after 8 h of treatment with G8 at concentrations >=10 mg/L. In a murine model of systemic cryptococcosis, G8 was effective at prolonging survival compared with the controls. Our data indicate that this new derivative has a potential therapeutic role in infections caused by C. neoformans.


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