Oxygenated Cyclohexene Derivatives from the Stem and Root Barks of Uvaria pandensis.

Gasper Maeda,Jelle Van Der Wal,Joan J E Munissi,Anastasia Rudenko,Per Sunnerhagen,Máté Erdélyi,Arvind Kumar Gupta,Stephen S Nyandoro,Pieter J Gilissen,Catarina Bourgard

doi:10.1021/acs.jnatprod.1c00811

Abstract

Five new cyclohexene derivatives, dipandensin A and B (1 and 2) and pandensenols A–C (3–5), and 16 known secondary metabolites (6–21) were isolated from the methanol-soluble extracts of the stem and root barks of Uvaria pandensis. The structures were characterized by NMR spectroscopic and mass spectrometric analyses, and that of 6-methoxyzeylenol (6) was further confirmed by single-crystal X-ray crystallography, which also established its absolute configuration. The isolated metabolites were evaluated for antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis and the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum, and Pseudomonas putida, as well as for cytotoxicity against the MCF-7 human breast cancer cell line. A mixture of uvaretin (20) and isouvaretin (21) exhibited significant antibacterial activity against B. subtilis (EC50 8.7 μM) and S. epidermidis (IC50 7.9 μM). (8′α,9′β-Dihydroxy)-3-farnesylindole (12) showed strong inhibitory activity (EC50 9.8 μM) against B. subtilis, comparable to the clinical reference ampicillin (EC50 17.9 μM). None of the compounds showed relevant cytotoxicity against the MCF-7 human breast cancer cell line.

Highlights

Five new cyclohexene derivatives, dipandensin A and B (1 and 2) and pandensenols A−C (3−5), and 16 known secondary metabolites (6−21) were isolated from the methanolsoluble extracts of the stem and root barks of Uvaria pandensis
The phytochemical constituents of the genus Uvaria include flavonoids3 and oxygenated cyclohexene derivatives, with the latter being restricted to the genus and its closely related genera within the Uvariae tribe,4−14 albeit with very few plant families other than Annonaceae.15−21 oxygenated cyclohexene derivatives have so far been reported from about 20 species of Uvaria4,6−9,14,22−28 and other genera of the Uvariae tribe such as Monanthotaxis,10,11,29 Ellipeiopsis,12,30 Dasymaschalon,31 Cleistochlamys,13,32 and Artabotrys
Our recent findings of the bioactive oxygenated cyclohexene derivatives including their chlorinated counterparts from Cleistochlamys kirkii13 and Monathotaxis trichocarpa11 inspired a reinvestigation of Uvaria pandensis Verdc., a plant species previously reported to contain similar compounds

Summary

Introduction

Dipandensin A and B (1 and 2) and pandensenols A−C (3−5), and 16 known secondary metabolites (6−21) were isolated from the methanolsoluble extracts of the stem and root barks of Uvaria pandensis. The 13C NMR data (Table 2, Figure S10, Supporting Information) of 2 consisted of a peak at δC 60.8 for a tertiary oxygenated carbon, assignable to C-1, instead of δC 135.2 observed for C-1 in 1. HRESIMS (Figure S24, Supporting Information) indicated a molecular ion [M + H]+ peak at m/z 281.1025 (calcd 281.1025), which along with the NMR data (Table 3)

Results

Conclusion