Background: Leishmaniasis is endemic in 98 countries and is closely associated with
poverty. On the basis of current evidence, it may be safely suggested that over time Leishmania
spp. have evolved coexistence in different macrophage types and developed adaptations in order to
ensure their intracellular survival. Considering new drugs, the need of the hour the present study
deals with the synthesis of novel compounds of biological importance based on naturally occurring
Objective: Synthesis, anti-leishmanial and anti-trypanosomal activities of a series of thirty three
(eighteen newly synthesized and fifteen previously reported) 7-arylbenzo[c]acridine-5,6-diones.
Method: A series of thirty-three 7-arylbenzo[c]acridine-5,6-diones was designed and synthesized.
The anti-leishmanial and anti-trypanosomal activities of the newly synthesized compounds were
Results: Seven compounds (14, 17, 19, 26, 27, 38 and 39) were found to exhibit excellent antiparasitic
activities. Compound 14 was identified as the most potent compound against L. donovani
promastigotes while compound 27 showed most significant inhibition activity against amastigotes.
Compounds 14 and 27 showed remarkable inhibitory activity with IC50 values of 0.38 and 0.53
µM, respectively, when tested in human macrophage cell line (THP) infected with L. donovani
amastigotes. Against trypanomastigotes, six compounds (15, 17, 19, 25, 26 and 43) demonstrated
Conclusion: Compound 19 was found to be the best anti-trypanosomal agent and showed 300-fold
superior inhibitory activity to that of the standard drug DFMO. Significant anti-leishmanial and
anti-trypanosomal activities combined with the non-cytotoxic profile presents 7-arylbenzo[c]acridine-
5,6-diones as new candidates with therapeutic potential in the treatment of parasitic diseases.