Bioactivity-Guided Optimization of 3-Deoxyanthocyanidin Extraction and Seasonal Mapping of Four Morphotypes of Fridericia chica (Bonpl.) L.G. Lohmann.

Ultrasound-assisted extraction (UAE) was combined with a design of experiments (DoE) to optimize the recovery of 3-deoxyanthocyanidins (3D-anths) from Fridericia chica leaves using in vitro antileishmanial activity against Leishmania amazonensis promastigotes as a bioactivity-guided response. A 3 × 3 factorial design evaluated extraction time (15-45 min) and ethanol concentration (70-100%), followed by HPLC-DAD quantification, cytotoxicity testing, and seasonal mapping of four morphotypes over 21 months. Ethanol concentration was the main determinant of extraction performance, and 100% ethanol produced the most active extracts. Assay C (15 min, 100% ethanol) showed the highest selectivity index (18.5); however, assay F (30 min, 100% ethanol) was selected through a supervised multi-criteria assessment because it combined favorable activity with the highest total 3D-anth content (12.58%) and carajurin recovery (10.37%). Chromatographic profiles remained qualitatively stable within morphotypes, although quantitative variation occurred among months. Carajurin predominated in AC1 and AC2, whereas 3'-hydroxy-carajurone predominated in AC3 and AC4. Most associations between the evaluated meteorological variables and 3D-anths content was not statistically significant; moderate negative correlations with relative humidity were detected for selected metabolites in AC1, AC2, and AC4. Hierarchical clustering produced four clusters consistent with the predefined morphotype classification in this dataset. These findings support UAE-DoE as a strategy for chemical standardization of F. chica extracts.