In vitro and in vivo anticryptococcal activities of a new pyrazolo-isothiazole derivative.
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 > or =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.
Barchiesi
Francesco
F
Istituto di Malattie Infettive e Medicina Pubblica, Università degli Studi di Ancona, Azienda Ospedaliera Umberto Io, Via Conca 60020, Torrette di Ancona, Ancona. emalinf@popcsi@unian.it
Milici
Maria E
ME
Arzeni
Daniela
D
Schimizzi
Anna M
AM
Pizzo
Giuseppe
G
Giammanco
Giovanni M
GM
Giannini
Daniele
D
Manfrini
Maurizio
M
Scalise
Giorgio
G
Vicentini
Chiara B
CB
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D000935:Antifungal Agents; D011720:Pyrazoles; D013844:Thiazoles