Atropisomeric 9,10-dihydrophenanthrene/bibenzyl trimers with anti-inflammatory and PTP1B inhibitory activities from Bletilla striata?

Organic & Biomolecular Chemistry Pub Date: 2022-05-25 DOI: 10.1039/D2OB00489E

Abstract

Two pairs of novel trimeric dihydrophenanthrene–bibenzyl–dihydrophenanthrene enantiomers (1 and2), the first examples of a dihydrophenanthrene dimer linked to a bibenzyl or dihydrophenanthrene through a C–O–C bond (3 and4), and a pair of rare polymers with a bibenzyl connected to C-8′ of the dihydrophenanthro[b]furan moiety via a methylene (5), together with four known compounds (6–9) were isolated from the tubers of Bletilla striata. Their structures including the absolute configurations were determined using spectroscopic data analysis and ECD and NMR calculations, combined with the exciton chirality method or the reversed helicity rule. The atropisomerism of dihydrophenanthrenes and related polymers was considered based on their chiral optical properties, and QM torsion profile calculations, which revealed the racemic mixture form of the polymers. Compounds 4, 5b, 6a and 7b significantly inhibited the production of NO in LPS-induced BV-2 cells, with IC50 values ranging from 0.78 to 5.52 μM. Further mechanistic study revealed that 7b suppressed the expression of iNOS, and suppressed the phosphorylation of the p65 subunit to regulate the NF-κB signaling pathway. Furthermore, compounds 2b, 5a, 5b, 7a and 7b displayed significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 3.43–12.30 μM.

Graphical abstract: Atropisomeric 9,10-dihydrophenanthrene/bibenzyl trimers with anti-inflammatory and PTP1B inhibitory activities from Bletilla striata
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