Elsevier

Fitoterapia

Volume 95, June 2014, Pages 34-41
Fitoterapia

Anti-HIV-1 tigliane diterpenoids from Excoecaria acertiflia Didr

https://doi.org/10.1016/j.fitote.2014.02.018Get rights and content

Abstract

Three tigliane-type diterpenoids named excoecafolins A–C and two daphnane-type diterpenoids named excoecafolins D and E, together with 13 known compounds, were isolated from the EtOAc extract of Excoecaria acerifolia Didr. Their structures were elucidated through the analysis of the spectroscopic data. The anti-HIV-1 activity evaluation of five of these compounds showed that four possessed moderate anti-HIV-1 activities with EC50 0.258, 0.036, 0.046, and 0.978 μM, SI > 1,836.9, 431.1, 298.7, and > 503.7, respectively. Additionally, the chemotaxonomic issue of the affinity correlation between Thymelaeceae and Euphorbiaceae is discussed based on the isolates.

Introduction

The relationship between the Thymelaeceae and Euphorbiaceae is controversial with both families categorized into different orders in the APG III [1]. Some systematists claimed that the two families (or elevated to be orders) were sister groups in the Malvales [2], [3], [4]. Nevertheless, characteristic tigliane and daphnane type diterpenoids isolated in both Thymelaeceae and Euphorbiaceae families serve as strong chemotaxonomic evidence for their affinity [5], [6]. In order to clearly define their relationships, other natural products from the two family species and the biosynthesis of daphnane diterpenoids need to be investigated. Excoecaria species (Euphorbiaceae), well known for living in mangrove and tropical rain forests, are used as traditional medicines in the south of China and Thailand as a uterotonic [7]. Previous studies focused on the common species of this genus such as Excoecaria agallocha and reported a great number of compounds including tigliane and daphnane-type diterpenoids [8], [9], [10], [11], [12]. Nowadays, daphnane and analogous diterpenoids are found to have remarkable biological activities, especially anti-HIV activity [9], [13], [14], [15]. Taken together, the study of the Excoecaria species can be very promising.

Excoecaria acerifolia Didr. is widely distributed in dry hot valleys of Southwest China as an epibiotic species in this genus [4]. It is usually used as the ethnodrug “Gua-jing-ban” by minority nationalities in Yunnan Province for its antiphlogistic, antidote, antitussive, anti-malaria, laxative, and anti-virus properties [16]. Diterpenoids were the main type of natural products of E. acerifolia [17] and some pimaranes were isolated from this plant in our previous studies [18], [19]. In a search for new bioactive tigliane and daphnane-type diterpenoids, our continuative investigation on natural products from E. acerifolia was carried out and five new tigliane and daphnane-type diterpenoids named excoecafolins A–E (15), along with 13 known compounds 618, were isolated from the EtOAc extract of E. acerifolia. The anti-HIV-1 activities of five isolates (14 and 6) were tested. Additionally, the relationship between Thymelaeceae and Euphorbiaceae is discussed on the basis of the compounds isolated, and the possible biogenetic pathways to daphnane diterpenoids. Herein, the isolation, structural elucidation, anti-HIV-1 activities, as well as chemotaxonomy discussion, are described.

Section snippets

General experimental procedures.

Optical rotations were measured on a Horiba SEPA-300 polarimeter, whereas UV spectra were obtained on a Shimadzu double-beam 210A spectrometer. IR spectra were obtained on a Tensor 27 spectrometer with KBr pellets. NMR spectra were acquired using a Bruker AV-400, a DRX-500, or AVANCE III-600 spectrometer with TMS as an internal standard. ESIMS and HRESIMS were obtained using an API QSTAR Pulsar 1 spectrometer, whereas EIMS and HREIMS were obtained using a Bruker HCT/Esquire and API Qstar

Results and discussion

The 95% EtOH extract prepared from the stems of E. acerifolia was suspended in water and then partitioned by petroleum ether and EtOAc, respectively. The EtOAc extract was subjected to repeated column chromatography over silica gel, Sephadex LH-20, and RP-18, and further purified by HPLC, to afford five new diterpenoids excoecafolins A–E (15) (Fig. 1), along with 13 known compounds, daphnopsis factor R2 (6) [21], 4-O-methyl-TPA (7) [22], 13-benzoate-phorbol (8) [22], [23], irritant factor M3 (9

Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (31300294), the Special Fund for Agro-scientific Research in the Public Interest (201303117), the National Support Science and Technology Subject (2013BAI11B04), and the Major Technology Project of Hainan (ZDZX2013008-4, ZDZX2013023-1). The authors thank Dr. Y.L. Huang (Department of Experimental Radiation Oncology, UT MD Anderson Cancer Center, USA) for initial proofreading of this paper and the members of

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