Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

doi:10.1007/s13659-019-0198-x

Natural Products and Bioprospecting ›› 2019, Vol. 9 ›› Issue (2): 157-163.DOI: 10.1007/s13659-019-0198-x

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Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

P. Annécie Benatrehina¹, Wei-Lun Chen³, Austin A. Czarnecki³, Steven Kurina³, Hee-Byung Chai¹, Daniel D. Lantvit³, Tran N. Ninh⁵, Xiaoli Zhang², Djaja D. Soejarto^3,4, Joanna E. Burdette³, A. Douglas Kinghorn¹, L. Harinantenaina Rakotondraibe¹

1 Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, College of Pharmacy, Columbus, OH, USA;
2 Center for Biostatistics, The Ohio State University, Columbus, OH, USA;
3 College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA;
4 John G. Searle Herbarium of the Field Museum of Natural History, Chicago, IL, USA;
5 Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology Hanoi, Hanoi, Vietnam

Received:2018-11-21 Revised:2019-01-28 Online:2019-04-04 Published:2019-04-24
Contact: L. Harinantenaina Rakotondraibe
Supported by:
This study was financially supported by the NIH/NCI through the Program Project P01(CA125066).The Podocarpus neriifolius root sample was acquired under a collaborative agreement between the University of Illinois at Chicago (USA) and the Institute of Ecology and Biological Resources of the Vietnam Academy of Science and Technology,Hanoi (Vietnam).The authors also thank Mr.Ermias Mekuria Addo and Dr.Craig McElroy,The Ohio State University,College of Pharmacy,Dr.Chunhua Yuan and Dr.Arpad Somogy,The Ohio State University Campus Chemical Instrument Center,for instrumentation access,assistance in acquiring MS and NMR data and for helpful discussions.

Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

1 Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, College of Pharmacy, Columbus, OH, USA;
2 Center for Biostatistics, The Ohio State University, Columbus, OH, USA;
3 College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA;
4 John G. Searle Herbarium of the Field Museum of Natural History, Chicago, IL, USA;
5 Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology Hanoi, Hanoi, Vietnam

通讯作者: L. Harinantenaina Rakotondraibe
基金资助:
This study was financially supported by the NIH/NCI through the Program Project P01(CA125066).The Podocarpus neriifolius root sample was acquired under a collaborative agreement between the University of Illinois at Chicago (USA) and the Institute of Ecology and Biological Resources of the Vietnam Academy of Science and Technology,Hanoi (Vietnam).The authors also thank Mr.Ermias Mekuria Addo and Dr.Craig McElroy,The Ohio State University,College of Pharmacy,Dr.Chunhua Yuan and Dr.Arpad Somogy,The Ohio State University Campus Chemical Instrument Center,for instrumentation access,assistance in acquiring MS and NMR data and for helpful discussions.

Abstract

Abstract: Bioactivity-guided phytochemical investigation of Podocarpus neriifolius D.Don.(Podocarpaceae) has led to the isolation of one new (2) and three known (1,3,and 4) B-type podolactones,along with three totarane-type diterpenes (5-7).Their structures were determined by interpretation of High Resolution ElectroSpray Ionization Mass Spectrometry (HRESIMS) and 1D and 2D NMR data,and comparison with the values reported in the literature.The structure of compound 1,previously identified as 3-deoxy-2a-hydroxynagilactone E (8),was revised as its 2β-epimer,which has been reported recently as a new compound.All of the isolates were evaluated for their antiproliferative activity against a panel of four human cancer cell lines,namely,ovarian (OVCAR3),breast (MDA-MB-231),colon (HT-29),and melanoma (MDA-MB-435),and compounds 1 and 3 were found to be cytotoxic with IC₅₀ values in the low micromolar range for most of the cell lines used.The major compound,inumakilactone A (3),was further tested in vivo using the HT-29,MDA-MB-435,and OVCAR3 cells in a murine hollow fiber model,for the first time.

Key words: Podocarpus neriifolius, Nagilactone G-2β-O-β-D-glucoside, Hollow fiber assay, 3-Deoxy-2α-hydroxynagilactone E, Antiproliferative, B-type podolactone

摘要： Bioactivity-guided phytochemical investigation of Podocarpus neriifolius D.Don.(Podocarpaceae) has led to the isolation of one new (2) and three known (1,3,and 4) B-type podolactones,along with three totarane-type diterpenes (5-7).Their structures were determined by interpretation of High Resolution ElectroSpray Ionization Mass Spectrometry (HRESIMS) and 1D and 2D NMR data,and comparison with the values reported in the literature.The structure of compound 1,previously identified as 3-deoxy-2a-hydroxynagilactone E (8),was revised as its 2β-epimer,which has been reported recently as a new compound.All of the isolates were evaluated for their antiproliferative activity against a panel of four human cancer cell lines,namely,ovarian (OVCAR3),breast (MDA-MB-231),colon (HT-29),and melanoma (MDA-MB-435),and compounds 1 and 3 were found to be cytotoxic with IC₅₀ values in the low micromolar range for most of the cell lines used.The major compound,inumakilactone A (3),was further tested in vivo using the HT-29,MDA-MB-435,and OVCAR3 cells in a murine hollow fiber model,for the first time.

关键词: Podocarpus neriifolius, Nagilactone G-2β-O-β-D-glucoside, Hollow fiber assay, 3-Deoxy-2α-hydroxynagilactone E, Antiproliferative, B-type podolactone

P. Annécie Benatrehina, Wei-Lun Chen, Austin A. Czarnecki, Steven Kurina, Hee-Byung Chai, Daniel D. Lantvit, Tran N. Ninh, Xiaoli Zhang, Djaja D. Soejarto, Joanna E. Burdette, A. Douglas Kinghorn, L. Harinantenaina Rakotondraibe. Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E[J]. Natural Products and Bioprospecting, 2019, 9(2): 157-163.

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Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

Bioactivity-Guided Isolation of Totarane-Derived Diterpenes from Podocarpus neriifolius and Structure Revision of 3-Deoxy-2α-hydroxynagilactone E

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