Elsevier

Phytochemistry

Volume 167, November 2019, 112081
Phytochemistry

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia

https://doi.org/10.1016/j.phytochem.2019.112081Get rights and content

Highlights

  • Five undescribed cyclopeptide alkaloids were isolated from Heisteria parvifolia Sm.

  • Their structures were elucidated by 1D, 2D-NMR and HR-ESI-MS analyses.

  • Their cytotoxicity against the chronic myeloid leukemia K562 cells was evaluated.

Abstract

Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in Côte d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.

Graphical abstract

Five undescribed cyclopeptide alkaloids from Heisteria parvifolia with interesting cytotoxic activity against chronic myeloid leukemia (K562) cell line.

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Introduction

Cyclopeptide alkaloids are widespread and occur in several families: Asteraceae, Celastraceae, Euphorbiaceae, Fabaceae, Menispermaceae, Olacaceae, Pandaceae, Rhamnaceae, Rubiaceae, Sterculiaceae, and Urticaceae (El-Seedi et al., 2007; Gournelis et al., 1997; Morel et al., 2009; Tan and Zhou, 2006). Previous studies have reported cyclopeptides alkaloids from Heisteria nitida (El-Seedi et al. 1999, 2005). The cyclopeptide alkaloids sensu stricto were classified according to the number of amino acid constituents outside and the size of the macrocycle (inside) as 4(13); 5(13); 4(14) and 4(15) type of alkaloids (Joullie and Richard, 2004; Tan and Zhou, 2006). Several activities of cyclopeptides alkaloids have been reported, such as antimicrobial (Gournelis et al., 1997; Morel et al., 2005), insecticidal (Sugawara et al., 1996), sedative (Suh et al., 1997), and antiplasmodiale activity (Suksamrarn et al., 2005).

The genus Heisteria belonging to the Olacaceae family comprises about 65 species in tropical America and 3 in Africa; namely Heisteria parvifolia Sm., Heisteria trillesiana Pierre ex Heckel, and Heisteria zimmereri Engl. Heisteria parvifolia Sm. is an evergreen shrub or small tree up to 15 (−20) m tall; 40 (−60) cm in diameter (Malaisse et al., 2004). H. parvifolia occurs from Senegal and south-western Mali eastward to the Central African Republic and southward DR Congo and northern Angola; possibly also in Uganda and southern Soudan (Louppe et al., 2008). In Côte d'Ivoire, is locally abundant on sandy soils. Its wood is used for construction and tool handles. In several areas, the fruits are eaten fresh; the small oil-rich seeds are eaten fresh, roasted or cooked. The twigs are used as chew-sticks. Various Heisteria species are used by South-American Indians or in Africa in the treatment of rheumatism, abscesses, headache, throat infections, swellings, nose bleedings, pain in joints and muscles, diarrhea, hepatic infection (Kvist and Holm-Nielsen, 1987; Russo, 1992; Tan and Zhou, 2006). In traditional medicine in Ghana, ground roots of H. parvifolia are applied as enema against stomach-ache. In Congo, sap from the root bark is used as dropps into the nose against migraine and into the eye to treat painful, infected eyes. Stem bark is taken in Ghana, in Côte d'Ivoire and DR Congo as cough medicine. In Gabon, bark is applied to circumcision wounds. In Ghana and Côte d'Ivoire, leaf decoctions are taken or applied as a bath to invigorate rachitic children and to treat convulsions. They are also used as analgesic and rubbed onto painful breasts of young mothers, and in Sierra Leone to treat tooth-ache. In Congo, leaf decoctions are administrated against asthma, costal pain, stomach pain, and menstrual problems. Ground seeds are used to stupefy fish. In DR Congo, powdered bark is an ingredient in the preparation of arrow poison (Abbiw, 1990; Burkill and families, 1997; Malaisse et al., 2004). Chemical investigations of Heisteria species have mainly revealed the presence of triterpenes and proanthocyanidines in H. pallida (Dirsch et al. 1992, 1993), cyclopeptide alkaloid in H. nitida (El-Seedi et al. 1999, 2005), scopolamine in H. olivae (Cairo-Valera et al., 1977), and acetylenic fatty acids in H. accuminata (Kraus et al., 1998). Up to date, only the composition of the seeds oil of H. parvifolia has been reported as mainly long-chain saturated fatty acids, oleic acid and other mono and di enoic fatty acids (Malaisse et al., 2004).

As a part of a continuing study for the discovery of medicinal Côte d'Ivoire species, five undescribed cyclopeptide alkaloids (15), together with one known compound (6), have been isolated and characterized from the leaves of H. parvifolia. Their cytotoxicity against the chronic myeloid leukemia K562 cells was evaluated.

Section snippets

Results and discussion

The crude alkaloid extract prepared with an acid-base method of air-dried and pulverized leaves of H. parvifolia was subjected to silica gel flash chromatography, eluted with increasingly polar mixtures of CHCl3/MeOH. Further purification was performed using semi-preparative HPLC. As a result, five undescribed cyclopeptide alkaloids (15) were isolated and chemically characterized, together with one known cyclopeptide alkaloids, anorldianine (6) (El-Seedi et al., 1999). Their structures (Fig. 1

Conclusion

In summary, six compounds were isolated from the crude alkaloid extract of H. parvifolia leaves, among them five previously undescribed cyclopeptide alkaloids from the 4(14) type, 4 amino acid constituents outside and the 14-atoms of the macrocycle (inside). Their structures were established by different spectroscopic methods including 1D and 2D-NMR experiments as well as HR-ESI-MS analysis. Compound 6 (anorldianine) that has a unique substructure containing proline, was previously isolated

General experimental procedures

Optical rotations were measured on a PerkinElmer model 341 polarimeter (589 nm, 20 °C). IR spectra were obtained on a Nicolet Avatar 320 FT-IR spectrometer with KBr disks. NMR spectra were acquired in CD3OD on Bruker Avance DRX III 500 instruments (1H at 500 MHz and 13C at 125 MHz). Standard pulse sequences and parameters were used to obtain 1D- (1H and 13C) and 2D- (COSY, ROESY, HSQC and HMBC) NMR spectra. HR-ESI-MS experiments were performed using a Micromass Q-TOF high-resolution mass

Cytotoxicity bioassay by MTS

K562 cells (chronic myeloid leukemia) were trypsinized, harvested, and spread onto 96-well flat-bottom plates at a density of 1000 cells per well, and then incubated for 24 h in RPMI 1640 Medium supplemented with 10% fetal bovine serum and antibiotics. After culture, the cells were treated with compounds 16 for 72 h. The cell cultures were then analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) according to the

Acknowledgements

The authors are grateful to Conseil Regional Champagne Ardenne, Conseil General de la Marne, Ministry of Higher Education, Research and Innovation (France) (MESRI) and EU-programme FEDER to the PlAneT CPER project for financial support as well as the Ministry of Research of Côte d’Ivoire.

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