Bioactive Tetrahydrofuran Lignans from Peperomia dindygulensis

Abstract

Five new tetrahydrofuran lignans (1-5), accompanied by four known compounds, were isolated from the ethyl acetate extract of Peperomia dindygulensis. Structures were elucidated mainly using 1D NMR, 2D NMR, and mass spectroscopic studies. The relative configurations of 1-5 were determined by NOE correlations. Several of the compounds showed weak growth inhibitory activity against three cell lines (WI-38, VA-13, and HepG2). Compound 5 exhibited stronger MDR (multidrug resistance) reversal activity than verapamil at 2.5 microg/mL in a cellular calcein accumulation assay. Compounds 4 and 5 showed weak inhibitory activity against induction of the intercellular adhesion molecule-1 (ICAM-1) in anti-inflammatory activity experiments.

Antibacterial Activity of a Virgatusin-Related Compound

“…Several reports regarding antibacterial activities of lignans have been published. [7][8][9][10][11] However, their themes have scarcely been focused on the relationship between absolute configuration of lignans and their bioactivities. It is interesting to find that the lignan with antibacterial activity required its absolute configuration for the expression of activity.…”

“…Some similar compounds have been isolated from plants. [3][4][5][6] Though the reversal of multidrug resistance by a similar tetrasubstituted tetrahydrofuran lignan has been reported, 7) the relationship between activity and stereochemistry was unknown. It is known that lignans have many kinds of biological activity 8,9) and some lignans had antibacterial activity, [8][9][10][11] however, biological research was performed by using compounds isolated from plants in many cases.…”

Antifungal Activity of Tetra-Substituted Tetrahydrofuran Lignan, (−)-Virgatusin, and Its Structure-Activity Relationship

“…The antibacterial activity of similar tetra-substituted tetrahydrofuran lignans was recently reported. 10,11) One of them, 10) the influence of stereochemistry and partial structures was unknown. The virgatusin-related compound having enantiomeric structure of (À)-virgatusin showed antibacterial activity in our previous study.…”

Biotransformation of a tetrahydrofuran lignan by the endophytic fungus Phomopsis Sp.

“…1 In particular, the optically active tetrahydrofuran lignans display a wide range of pharmacological activities, including anti-parasite, [2][3][4] antibacterial, 5 antifungal, 6 antitumoral, 7 anti-inflammatory 8,9 and platelet-activating factor (PAF) inhibition. [10][11][12] Several non-symmetrical 2,5-diaryltetrahydrofuran lignans, shown in Table 1, have been isolated from Piper species (Piperaceae) containing either piperonyl, veratryl or 3,4,5-trimethoxyphenyl substituent at 2 and 5 positions and methyl groups at 3 and 4 positions attached to the tetrahydrofuran ring, as illustrated by (+)-calopiptin (1, P. schmidtii), 5-[rel-(2S,3S,4S,5S)-5'-(3'',4''-dimethoxyphenyl)-3',4'-dimethyl-2'-tetrahydro-furanyl)]-1,3-benzodioxole (2, P. wightii), (2S,3R,4S,5R)-3,4-dimethyl-2,5-bis(3',4'-dimethoxyphenyl)-tetrahydrofuran (3, P. clarkii), (±)-galgravin (4, P. futokadsura, P. hancei, P. puberculum, P.wallichii), (-)-galbelgin (5, P. attenuatum, P. futokadsura, P. thomsoni, P. wightii), (+)-grandisin (6, P. polysyphorum), (+)-machilin G (7, P. schmidtii, P. wightii), (+)-veraguensin (8, P. cuneifolium, P. futokadsura, P. puberculum) and (-)-zuonin A (9, P. schmidtii).…”