Title : Flavonoids from Piper longicaudatum as antifungal agents against Passiflora phytopathogens
Abstract:
In Colombia, the cultivation of Passiflora species such as gulupa (Passiflora edulis f. edulis), sweet granadilla (P. ligularis) and yellow passion fruit (P. edulis f. flavicarpa) represents an economically important agricultural sector, supported by increasing demand in international markets, particularly in the European Union. However, crop productivity and fruit quality are frequently affected by phytopathogenic fungi throughout pre- and post-harvest stages. Disease management relies largely on synthetic fungicides, whose intensive use may generate environmental impacts and challenges associated with pesticide residues and export requirements. Consequently, there is a growing need to identify effective and sustainable antifungal alternatives from natural sources. This study aimed to evaluate the antifungal potential of Piper longicaudatum against phytopathogenic fungi associated with Passiflora crops. An ethanolic extract obtained from the inflorescences of P. longicaudatum was evaluated against Colletotrichum colombiense, Fusarium triseptatum, Alternaria alternata, and Cladosporium cladosporioides using mycelial growth inhibition assays. The crude extract was subsequently fractionated, and the resulting fractions were evaluated under the same experimental conditions. The ethanolic extract inhibited the growth of all evaluated phytopathogens, with half-maximal inhibitory concentration (IC??) values ranging approximately from 100 to 600 µg/mL, indicating differences in susceptibility among fungal species. Fractionation enhanced the antifungal response, and the dichloromethane fraction exhibited the most promising activity, with IC?? values in the approximate range of 75–170 µg/mL. This fraction was therefore selected for purification by flash chromatography, leading to the isolation and identification of four active flavonoids belonging to the dihydrochalcone and flavanone subclasses. The isolated metabolites showed variable antifungal effects, with mycelial growth inhibition ranging approximately from 30% to 100% against the evaluated susceptible phytopathogens. To further investigate the structural features associated with antifungal activity, a structure–activity relationship analysis was performed by comparing the isolated metabolites with six additional flavonoids previously obtained from other Piper species or through chemical synthesis. The comparative analysis indicated that the flavonoid scaffold and oxygenation pattern substantially influenced antifungal activity, with selected flavanone structures displaying greater inhibitory potential than structurally related dihydrochalcones. These findings highlight P. longicaudatum as a promising source of antifungal flavonoids and provide a basis for the development of natural alternatives for the management of fungal diseases affecting Passiflora crops. Ongoing studies are focused on expanding the chemical series through synthesis and determining the antifungal potency of individual compounds to further establish structure–activity relationships. This study was funded by the Sistema General de Regalías of Colombia under project BPIN 2023000100058. Research activities on Colombian biodiversity were conducted under Genetic Resource Access Contract No. 121 of January 22, 2016, and its Amendment (Otrosí) No. 21, executed between the Ministerio de Ambiente y Desarrollo Sostenible and the Universidad Nacional de Colombia.
