Sleeping sickness, caused by trypanosomes, is a debilitating,
neglected tropical disease wherein current treatments suffer
from several drawbacks such as toxicity, low activity, and
poor pharmacokinetic properties, and hence the need for
alternative treatment is apparent. To this effect, we
screened in vitro a library of 2-quinazolinone derivatives
for antitrypanosomal activity against T.b. brucei and
cytotoxicity against HeLa cells. Seven compounds having no
overt cytotoxicity against HeLa cells exhibited
antitrypanosomal activity in the range of 0.093–45 µM were
identified. The activity data suggests that the
antitrypanosomal activity of this compound class is amenable
to substituents at N1 and C6 positions. Compound 14
having a molecular weight of 238Da, ClogP value of 1 and a
total polar surface area of 49 was identified as the most
active, exhibiting an IC50 value of 0.093 µM
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Abstract.
Synthesis and characterization of 1,2,3-triazole integrated quinazolinone derivatives