A new bicyclo[3.2.1]octanoids neolignan from Piper crocatum and evaluation of antimicrobial and antibiofilm activities

Piper crocatum, traditionally used in Indonesia as a natural antiseptic, remains underexplored chemically. In this study, four neolignans were isolated from its leaves, including a new bicyclo[3.2.1]octanoid neolignan, 4,5-methylenedioxy-2'-acetyl-nectamazin C (2) and three known analogues: rel-(1'R,5'S,6'R,7S,8R)-Δ2',8'-6'-acetoxy-3,3',5'-trimethoxy-4,5-methylenedioxy-4'-oxo-8.1',7.5'-neolignan (1), crocatin A (3) and crocatin B (4). All compounds share the rare bicyclo[3.2.1]octanoid neolignane framework. Structures were elucidated using UV, FT-IR, 1D and 2D NMR, ECD, and mass spectrometry. Antimicrobial activity was evaluated against Streptococcus mutans and Candida albicans. Compounds 1 and 2 showed weak activity, with the same minimum inhibitory concentrations (MICs) of 2.5 mg/ml (5.6 µM) against S. mutans and 1.25 mg/ml (2.8 µM) against C. albicans. Meanwhile, compounds 1-4 reduced biofilm by more than 50% at a concentration of 500 μg/ml (≈1.1 mM, depending on molecular weight). These findings contribute to the chemical profile of P. crocatum and enrich the scaffold types of neolignans.