Anti-fungal and anti-leishmanial activities of pectin-amphotericin B conjugates

Citrus pectin was oxidized using periodate and amphotericin B (AmB), a water-insoluble polyene antibiotic was conjugated via imine linkage to the oxidized pectin in borate buffer (pH 11) at-20 wt% concentration. The imine conjugate was reduced using sodium borohydride to give the more stable amine conjugates. The AmB conjugates were evaluated for their anti-fungal activity against C albicans and A. fumigatus. The minimum inhibitory concentration (MIC) against C albicans was 0.19 mu g/mL for both pectin-AmB imine and amine conjugates whereas the MIC against A. fumigatus was 6.25 mu g/mL for imine conjugates and 25 nimLfor amine conjugates. The conjugates also exhibited potent antileishmanial activity against different strains of L donovani in culture. The IC50 (inhibitory concentration 50%) values for the imine and amine conjugates against L. donovani LV9 intramacrophage amastigote were 0.25 +/- 0.02 mu L and 0.13 +/- 0.02 mu g/mL, respectively in comparison to a value of 0.03 +/- 0.01 mu g/mL for pure AmB whereas the values were 0.12 +/- 0.01 and 1.18 +/- 0.11 mu g/mL for the imine and amine conjugates against L. donovani DDB. While pure AmB produced 71% hemolysis to human blood at a concentration of 10 ligImL, the pectin-AmB conjugates exhibited negligible hemolytic activity showing only 0.6-0.9% hemolysis at an AmB concentration of 100 mu g/mL. The conjugates were soluble in water and were stable during storage in their dry form. The amine conjugate was able to reverse AmBresistance in Leishmania. This promising data and the unexpected observation that the amine conjugate was more active than the imine conjugate requires further mechanistic studies. (C) 2017 Elsevier B.V. All rights reserved.