Chemical constituents of Guarea glabra: a new alkaloid, a new dihydro-α-pyrone, and antitrypanosomal pimarane-type diterpenes.

Chemical investigation of the methanolic extract of Guarea glabra Vahl (Meliaceae) led to the isolation of a new amide alkaloid containing a pyrrolidine moiety (1) and a dihydro-α-pyrone derivative (2), together with two known pimarane-type diterpenes (3, 4). The structures of the new compounds were elucidated using comprehensive spectroscopic analyses, including 1D and 2D NMR experiments. The absolute configuration of 2 was determined by comparing experimental and calculated electronic circular dichroism spectra. Compounds 1-4 demonstrated antitrypanosomal activity against the epimastigote form of Trypanosoma cruzi, with IC50 values ranging from 0.66 to 2.3 µM; compound 4 exhibited submicromolar activity. In the intracellular assay, compound 3 reduced the number of intracellular amastigotes at 10 µM. None of the isolated compounds showed significant antimalarial activity under the tested conditions. Compounds 1-4 exhibited favorable selectivity for T. cruzi over mammalian HT1080 cells. These findings highlight pimarane-type diterpenes as structurally distinct, sp3-rich scaffolds with favorable selectivity profiles and potential as leads for the development of new antitrypanosomal agents.