Cytotoxic Phenanthrene, Dihydrophenanthrene, and Dihydrostilbene Derivatives and Other Aromatic Compounds from Combretum laxum.

Eder Bisoli,Maria de Fátima Cepa Matos,Renata Trentin Perdomo,Walmir Silva Garcez,Fernanda Rodrigues Garcez,Talita Vilalva Freire,Lyara Meira Marinho Queiróz,Nídia Cristiane Yoshida

doi:10.3390/molecules25143154

Eder Bisoli, Maria de Fátima Cepa Matos + Show 6 more

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https://doi.org/10.3390/molecules25143154

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Abstract

The chemical investigation of the roots and stems of Combretum laxum yielded a new dihydrostilbene derivative, 4′-hydroxy-3,3′,4-trimethoxy-5-(3,4,5-trimethoxyphenoxy)-bibenzyl (1), two phenanthrenes (2–3), and three dihydrophenanthrenes (4–6), along with one lignan, three triterpenoids, one aurone, one flavone, one naphthoquinone, and two benzoic acid derivatives. Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic techniques and/or mass spectrometry data. The occurrence of dihydrostilbenoid, phenanthrene and dihydrophenanthrene derivatives is unprecedented in a Combretum species native to the American continent. 2,7-Dihydroxy-4,6-dimethoxyphenanthrene, 2,6-dihydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene and 5-O-methyl apigenin are novel findings in the Combretaceae, as is the isolation of compounds belonging to the chemical classes of aurones and naphthoquinones, while (+)-syringaresinol is reported for the first time in the genus Combretum. Compounds 1–6 were also evaluated for their in vitro cytotoxicity against five human cancer cell lines, and radical-scavenging ability against 1,1-diphenyl-2-picryl-hydrazyl (DPPH). 6-Methoxycoelonin (4) was the most cytotoxic against melanoma cells (IC50 2.59 ± 0.11 µM), with a high selectivity index compared with its toxicity against nontumor mammalian cells (SI 25.1). Callosin (6), despite exhibiting the strongest DPPH-scavenging activity (IC50 17.7 ± 0.3 µM), proved marginally inhibitory to the five cancer cell lines tested, indicating that, at least for these cells, antioxidant potential is unrelated to antiproliferative activity.

Highlights

The genus Combretum, found in tropical and subtropical areas, is the largest within the Combretaceae and most of its species are extensively used in the folk medicine of African and Asian countries for the treatment of a wide variety of health disorders [1,2,3]
EtOH extract from the roots of C. laxum, compounds 1–7, and 13–15, comprising phenanthrenes, dihydrophenanthrenes, dihydrostilbene, lignan, and triterpenes (Figure 1), were obtained
Among the one new and 14 known compounds comprising nine different classes of secondary metabolites, the isolation of dihydrostilbenoid, phenanthrene and dihydrophenanthrene derivatives is unprecedented in a Combretum species native to the American continent

Summary

Introduction

The genus Combretum, found in tropical and subtropical areas, is the largest within the Combretaceae and most of its species are extensively used in the folk medicine of African and Asian countries for the treatment of a wide variety of health disorders [1,2,3]. 20 genera comprising the Combretaceae, the genus Combretum is notable for providing a number of classes of biologically active chemical constituents. In the course of the chemical investigation on Brazilian plants from the Pantanal, we previously reported the isolation of 11 triterpenoid derivatives from the stems of C. laxum [8]. We describe the isolation of the new dihydrostilbenoid 40 -hydroxy-3,30 ,4-trimethoxy-5(3,4,5-trimethoxyphenoxy)-bibenzyl (1), the phenanthrenes 2,7-dihydroxy-4,6-dimethoxyphenanthrene (2) and 2,6-dihydroxy-3,4,7-trimethoxyphenanthrene (3), the dihydrophenanthrenes 6-methoxycoelonin (4), 2,6-dihydroxy-3,4,7-trimethoxy-9,10-dihydrophenanthrene (5), and callosin (6), and the lignan syringaresinol (7) from its roots, in addition to the triterpenoids arjunolic (13), betulinic (14) and maslinic (15) acids—two of which were already described in our former study on the stems of C

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