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Planta Med 2018; 84(12/13): 913-919
DOI: 10.1055/a-0608-4946
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antiprotozoal Diterpenes from Perovskia abrotanoides [*]

Marzieh Tabefam
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
2   Division of Pharmaceutical Biology, University of Basel, Switzerland
,
Mahdi Moridi Farimani
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
,
Ombeline Danton
2   Division of Pharmaceutical Biology, University of Basel, Switzerland
,
Justine Ramseyer
2   Division of Pharmaceutical Biology, University of Basel, Switzerland
,
Marcel Kaiser
3   Swiss Tropical and Public Health Institute, Basel, Switzerland
4   University of Basel, Basel, Switzerland
,
Samad N. Ebrahimi
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
,
Peyman Salehi
1   Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran
,
Hossien Batooli
5   Kashan Botanical Garden, Research Institute of Forests and Rangelands, Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran
,
Olivier Potterat
2   Division of Pharmaceutical Biology, University of Basel, Switzerland
,
Matthias Hamburger
2   Division of Pharmaceutical Biology, University of Basel, Switzerland
› Author Affiliations
Further Information

Publication History

received 19 January 2018
revised 22 March 2018

accepted 12 April 2018

Publication Date:
26 April 2018 (online)

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Abstract

As part of a screening for new antiparasitic natural products from Iranian plants, n-hexane and ethyl acetate extracts from the aerial parts of Perovskia abrotanoides were found to exhibit strong inhibitory activity against Trypanosoma brucei rhodesiense and Leishmania donovani. The activity was tracked by high-performance liquid chromatography (HPLC)-based activity profiling. Preparative isolation by a combination of silica gel column chromatography and HPLC afforded 17 diterpenoids (1–17), including 14 abietane-, two icetexane-, and one isopimarane-type derivatives. Among these, (5R,10S)-11-hydroxy-12-methoxy-20-norabieta-8,11,13-triene (2), 12-hydroxy-norabieta-1(10),8,11,13-tetraene-1,11-furan (6), and 12-methoxybarbatusol (9) were new compounds, the structure of which was established by comprehensive spectroscopic data analysis (one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism). The antiprotozoal activity of the isolated compounds was evaluated against T. b. rhodesiense, Trypanosoma cruzi, L. donovani, and Plasmodium falciparum. Selectivity indexes (SI) were calculated in comparison to cytotoxicity on rat myoblast (L6) cells. Particularly active were 7α-ethoxyrosmanol (4) with an IC50 of 0.8 µM against T. b. rhodesiense (SI 14.9) and an IC50 of 1.8 µM (SI 6.9) against L. donovani, ferruginol (8) with an IC50 of 2.9 µM (SI 19.2) against P. falciparum, and miltiodiol (10) with an IC50 of 0.5 µM (SI 10.5) against T. b. rhodesiense. None of the compounds exhibited selective toxicity against T. cruzi (SI ≤ 1.6).

Key words

Perovskia abrotanoides - Lamiaceae - diterpenoids - Leishmania donovani - Trypanosoma brucei rhodesiense - Plasmodium falciparum

* Dedicated to Professor Dr. Robert Verpoorte in recognition of his outstanding contribution to natural products research.


Supporting Information

    HPLC-activity profiling of n-hexane and ethyl acetate extracts against T. b. rhodesiense and L. donovani, 1D and 2D NMR spectra of compound 6, 1H and 2D NMR spectra of compounds 2 and 9, HRESIMS spectra of compounds 2, 6, and 9, NOESY, and ROESY spectra of compounds 15 and 16, 1H-NMR data, and 13C-NMR data (extracted from HSQC-DEPT and HMBC spectra) for all known compounds are available as Supporting Information.

  • Supporting Information
 

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