Screening of Anti-Infectives against Leishmania donovani
2016
Aim: To evaluate in vitro the
effectiveness of several anti-infective agents alone and in combination against Leishmania donovani. Method: A convenient stratified sampling method
was used to obtain selected anti-infective agents. For individual drug samples,
Half Maximal Inhibitory Concentrations (IC50) were obtained using the
broth dilution method. The IC50’s of the drugs which were active against L. donovani were used as reference
values to prepare drug combinations for the modified microdilution checkerboard
method. Results: Five
(5) out of the fifty-six (56) drugs used showed activity (inhibition of cell growth)
against L. donovani cells. They include
Quinine sulphate (IC50 = 0.089 μg/ml), gentamicin (IC50 =
8.1 μg/ml), amodiaquine (IC50 = 138 μg/ml) and the two standard drugs:
Amphotericin B (IC50 = 6.3 μg/ml) and Pentamidine (IC50 =
25 μg/ml). The remaining fifty-one (51) drugs did not show any inhibition within
the range of concentrations used (1.25 - 160 μg/ml). The drug combinations of Pentamidine/Amodiaquine,
Pentamidine/ Quinine sulphate, Pentamidine/Gentamicin, Amphotericin B/Quinine Sulphate,
Amphotericin B/ Gentamicin, Amodiaquine/Quinine sulphate and Amodiaquine/Gentamicin
showed synergistic effects against L. donovani whereas the Amphotericin B/Amodiaquine combination was antagonistic. Notable
in the results obtained was the high effectiveness of quinine sulphate in inhibiting
the growth of L. donovani. Quinine sulphate,
though not indicated for leishmania treatment, was more effective than the two standard
drugs and has a potential of playing a significant role in the treatment of leishmaniasis. Conclusion: This study has revealed five (5) anti-infective agents that by
themselves or in combinations show activity against L. donovani. Some of the drug combinations which showed synergism should
further be investigated. These results have to be confirmed by in vivo studies to define their roles in
leishmaniasis treatment.
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