Improving the drug-likeness of inspiring natural products - evaluation of the antiparasitic activity against Trypanosoma cruzi through semi-synthetic and simplified analogues of licarin A.

ABSTRACT: Neolignan licarin A (1) was isolated from leaves of Nectandra oppositifolia (Lauraceae) and displayed activity against trypomastigote forms of the etiologic agent of American trypanosomiasis, Trypanosoma cruzi. Aiming for the establishment of SAR, five different compounds (1a - 1e) were prepared and tested against T. cruzi. The 2-allyl derivative of licarin A (1d) exhibited higher activity against trypomastigotes of T. cruzi (IC₅₀ = 5.0 μM and SI = 9.0), while its heterocyclic derivative 1e displayed IC₅₀ of 10.5 μM and reduced toxicity against NCTC cells (SI > 19.0). However, these compounds presented limited oral bioavailability estimation (<85%, Papp <1.0 × 10^-6 cm/s) in parallel artificial membrane permeability assays (PAMPA) due to excessive lipophilic

SUBMITTER: Morais TR 

PROVIDER: S-EPMC7096397 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature