In vitro antifungal activity of aryl sulfonamides derivatives from amino alcohols
Sulfonamides. Aminoalcohols. N-tosylation. Reduction. MIC. Candida spp.
T. asahii.
Fungi are eukaryotic organisms with a membrane and a cell wall. They are
components of human's natural microbiota, however, in last decade several new cases
of severe fungal infections have been reported. In this scenario, species of Candida
spp. and Trichosporon asahii demonstrate clinical importance. The insertion of
sulfonamides group is attractive in drug design and several examples of sulfonamides
derivatives have been evaluable in drugs on the market. Another important bioactive
class is aminoalcohols derivatives which are members of several molecules of natural
products and drugs. Thus, 15 p-methylbenzylsulfonamides derived from four essential
amino acids (phenylalanine, leucine, proline and glycine) and commercial
aminoalcohols were synthesized. N-tosylation of aminoacids 1a-d afforded the
products 2a-d with good yields. Derivatives 3a-c were obtained by reduction of 2a-c
with borane in THF, with satisfactory yields. Finally, 3d-k were synthesized at low
yields by the N-tosylation of commercial aliphatic aminoalcohols. The structures were
confirmed by IR and NMR spectroscopy. The 15 derivatives were then tested (0.60-
0.035 mM) against six species of Candida spp. (C. albicans, C. dubliniensis, C.
glabrata, C. krusei, C. parapsilosis, C. tropicalis) and Trichosporon asahii. The MICs
were determined in microplate by a sensitivity test, after incubation at 37ºC for 48 h.
The results showed that just 3d was unable to inhibit T. assahi growth, 3a and 3i
inhibited four species of Candida spp., including C. albicans while 2a, 2b, 2c, 2d, 3c,
3e, 3e ', 3f, 3g, 3j, 3k of Candida spp. and T. asahii. Finally, 3d and 3h were active
only against two species. In general, the reduction of carboxylic acid to alcohol function
improved the antifungal action by amplifying the action spectrum of the precursors (2a
and 2c). 3a (0,60-0,15mM), 3i (0,60-0,15mM) and 3j (0,60-0,075mM) showed greater
potential among the synthesized products. Overall, derivatization of aminoalcools with
sulfonamide by N-tosylation has been produce active derivatives especially against
Candida non-albicans.