Antifungal and immunomodulating activities of 1,4-benzothiazine azole derivatives: review.
We reviewed the studies on the in vitro and in vivo antifungal activity of 1,4-benzothiazine azole derivatives (1,4-BT). A number of different 1,4-BT have been tested for anti-Candida activity, investigating their N-4 substitution, sulfur oxidation state, presence of the carbonyl group in C-3, insertion of the side chain on C-6, C-7 or C-8 of benzothiazine nucleus, the nature of azolic substituent (triazole or imidazole), which tend to differ. Moreover, benzoxazine analogues have been tested to evaluate the effect of sulfur bioisosteric substitution on their activity. We found that their antifungal activity correlates with well-defined chemical characteristics including the presence of ether substitution at the side chain. In fact, ether derivatives are the most active compounds in vivo, although they have little anti-Candida effect in vitro. This discrepancy could be attributed to the fact that 1,4-BT are metabolized to active antifungal compounds and may have in vivo activity through improvement of protective immune response and direct antifungal effects. In fact, 1,4-BT also show immunomodulating activity so that the direct antifungal activity, in combination with the capability to stimulate the immune response, could result in a significant increase in in vivo efficacy.
Department of Drug Chemistry and Technology, University of Perugia, Italy. fringuel@unipg.it
R
R
Fringuelli
F
F
Schiaffella
A
A
Vecchiarelli
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000382:microbiology; D004464:Econazole / Q000737:chemistry / Q000494:pharmacology*; D015725:Fluconazole / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001393:Azoles; D004464:Econazole; D015725:Fluconazole