Structural Elucidation of the Cyclopeptide Papaucin Isolated From <scp> <i>Annona diversifolia</i> </scp> Saff. Seeds by NMR, Antiprotozoal Activity and Molecular Docking Studies

The hydroethanolic extract obtained from the seeds of Annona diversifolia Saff (Annonaceae) fruits was analyzed to obtain a new cycloheptapeptide, called papaucin (1) or cyclo(-Pro¹-Val²-Ile³-Thr⁴-Asn⁵-Leu⁶-Gly⁷-). Its molecular structure was determined using 1D and 2D NMR spectroscopic techniques (¹H, ¹³C, HSQC, COSY, HMBC, and TOCSY) and MALDI-TOF mass spectrometry. Additionally, the antiprotozoal activity was evaluated. Papaucin (1) showed moderate positive activity compared with in vitro assays of Entamoeba histolytica and Giardia lamblia, with IC₅₀ values of 63.07 and 67.62 μg mL^-1 respectively. On the other hand, in silico studies revealed a higher affinity of papaucin for the PFOR enzyme compared with metronidazole, as evidenced by a greater number of polar interactions. Regarding the ALR enzyme, papaucin also showed affinity, although at a binding site different from the main catalytic site. These results suggest that papaucin could exert its antiprotozoal effect through multiple mechanisms.