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Searching for novel leishmanicidal compounds with innovative structural scaffold, we designed a new series of hybrid compounds based on the structures of piperine and chlorogenic acid, two known natural products reported for their activities against different species of Leishmania. It was synthesized new thirteen piperonyl-cinnamoyl hybrids, which were preliminarly evaluated for their leishmanicidal activity on the promastigote forms of Leishmania amazonensis. The screening results revealed that almost all tested compounds were active. In particular, compounds PQM-287, 284 and 285 exhibited the higher potencies against the parasites, with IC50 values of 1.3, 2.75 and 3.85 µg/mL, highlighting the promising profile of action of this series. Αn In silico study for physicochemical properties and Pharmacokinetic parameters suggested their good druggability and bioavailability. The most promising compounds are being additionally evaluated against amastigote forms of L. amazonensis, as well as their possible mechanism of action previously to a next in vivo study.
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