Structural Elucidation of the Cyclopeptide Papaucin Isolated From Annona diversifolia 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.