title: Antidermatophytic activity of pyrazolo[3,4-c]isothiazoles: a preliminary approach on 4-chlorophenyl derivative for evaluation of mutagenic and clastogenic effects on bacteria and human chromosomes in vitro.
abstract: The antifungal activity of eight pyrazolo[3,4-c]isothiazole derivatives was evaluated on five dermatophytes: three were of an anthropophilic species (i.e., Epidermophyton floccosum, Trichophyton rubrum, and Trichophyton tonsurans) and two were of a geophilic species (i.e., Microsporum gypseum and Nannizzia cajetani). The new compounds proved to be unlikely effective in inhibiting the growth of the different strains. In general, the fungi parasitic on man were more sensitive than the geophilic species. This fact can be positive for a possible practical-therapeutic utilization of this class of compounds. To verify their possible use against fungi of medical interest, the most interesting substance at low doses, 6-(4-chlorophenyl)-4-methyl-6H-pyrazolo[3,4-c]isothiazol-3-amine, was chosen to perform in vitro genotoxicity tests using the following: Salmonella/microsome test (SAL), sister chromatid excange test (SCE), cytokinesis-blocked micronucleus test (CBMN), and its improvement (Ara-C/CBMN). The compound showed no mutagenic activity at low doses, whereas at the highest dose (100 µg/mL), it caused a generalized cytotoxic effect. The high growth inhibition exerted on fungi at the lowest dose and the concomitant lack of genotoxicity, at least until the dose of 50 µg/mL, might suggest the compound as a safe candidate as an antidermatophytic substance.
authors.affiliation: Dipartimento di Biologia ed Evoluzione, Sezione di Risorse Agrotecnologiche e Farmaceutiche, Università di Ferrara, Ferrara, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rossi
authors.forename: Donatella
authors.initials: D
authors.lastname: Mares
authors.forename: Carlo
authors.initials: C
authors.lastname: Romagnoli
authors.forename: Elisa
authors.initials: E
authors.lastname: Andreotti
authors.forename: Stefano
authors.initials: S
authors.lastname: Manfredini
authors.forename: Chiara Beatrice
authors.initials: CB
authors.lastname: Vicentini
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D003883:Arthrodermataceae / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008826:Microbial Sensitivity Tests; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*
chemical_list: C561432:6-(4-chlorophenyl)-4-methyl-6H-pyrazolo(3,4-c)isothiazol-3-amine; D000935:Antifungal Agents; D009153:Mutagens; D011720:Pyrazoles; D013844:Thiazoles