Planta Med 2016; 82(S 01): S1-S381
DOI: 10.1055/s-0036-1596515
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Antiproliferative diterpenoids from the roots of Podocarpus neriifolius

PA Benatrehina
1   Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 W. 12th Ave, Columbus, Ohio 43210, United States
,
TN Ninh
2   Institute of Ecology and Biological Resources, Vietnam academy of science and Technology, Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam
,
C Slebodnick
3   Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, 1981 Kraft Drive, Blacksburg, Virginia 24061, United States
,
DD Soejarto
4   Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, United States
5   Science and Education, Field Museum of Natural History, 1400 S. Lake Shore Dr., Chicago, Illinois 60605, United States
,
LH Rakotondraibe
1   Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 W. 12th Ave, Columbus, Ohio 43210, United States
,
AD Kinghorn
1   Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 W. 12th Ave, Columbus, Ohio 43210, United States
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2016 (online)

 

Plant samples collected in the Southeast Asian rainforests were subjected to initial screening against the HT-29 human colon cancer cell line, and Podocarpus neriifolius D. Don (Podocarpaceae), obtained from Vietnam, with an IC50 value of 8.2 µg/mL, was selected for further investigation aiming for the discovery of potential anticancer lead agents. Bioactivity-guided purification of the active ethyl acetate fraction (IC50= 4.3 µg/mL) from the dried root sample of P. neriifolius has so far afforded three type-B podolactones, namely, makilactones E (1) and G (2) and inumakilactone A (3), all characterized by the presence of a 7α,8α-epoxy-9(11)-enolide functionality [1 – 3]. Their structures were determined by interpretation of spectroscopic data and comparison with the existing literature [1,2]. In addition, the X-ray crystallography data of 1 was obtained to confirm its absolute configuration. While 3 has shown termiticidal and cytotoxic activity against murine leukemia cells P388 in vitro [1,2], in this study, it exhibited potent activity against HT-29 with an IC50 value of 1.1µM. On the other hand, compounds 1 and 2 were non-cytotoxic in this assay. In this presentation, the isolation and structure determination of these compounds are described as well as the dereplication of additional active sub-fractions, which suggests the presence of different active podolactones and totarane-type diterpenes.

Acknowledgements: Financial Support for this project was provided by the U.S. National Cancer Institute (NCI), National Institute of Health (NIH) through a program project 2P01 CA125066 awarded to Prof. A. Douglas Kinghorn.

Keywords: Podocarpus, neriifolius, podolactones, HT-29.

References:

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[2] Ito S, Kodama M, Sunagawa M, Takahashi T, Imamura H, Honda O. Structure of inumakilactone A, a bisnorditerpenoid. Tetrahedron Lett 1968; 17: 2065 – 2070

[3] Barrero AF, Quilez Del Moral JF, Mar Herrador M. Podolactones: a group of biologically active norditerpenoids. Stud Nat Prod Chem 2003; 28: 453 – 516