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Mar. Drugs 2018, 16(1), 15; doi:10.3390/md16010015

Aquaculture Soft Coral Lobophytum crassum as a Producer of Anti-Proliferative Cembranoids

1
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University (NSYSU), 70 Lien-Hai Road, Kaohsiung 80424, Taiwan
2
Doctoral Degree Program in Marine Biotechnology, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan
3
National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan
4
Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 94450, Taiwan
5
Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo 11566, Egypt
6
Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11432, Egypt
7
General Study Center, National Kaohsiung Marine University, Kaohsiung 80543, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 22 November 2017 / Revised: 14 December 2017 / Accepted: 19 December 2017 / Published: 7 January 2018
(This article belongs to the Special Issue Natural Products from Coral Reef Organisms)
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Abstract

Our continuous search for marine bioactive secondary metabolites led to the screening of crude extracts from a variety of aquaculture soft corals. The ethyl acetate (EtOAc) extract of Lobophytum crassum showed a distinctive chemical profile that was different from the wild type. It demonstrated significant anti-proliferative activity against Molt 4 leukemia cell with an IC50 value of 1 μg/mL after 24 h. Chemical investigation focusing on the unique peaks in L. crassum profile led to the discovery of a new α-tocopherol crassumtocopherol C (1), and two new cembrane-based diterpenoids culobophylins D (2) and E (3), along with ten known cembranoids (413). The structures of these isolates were elucidated using extensive spectroscopic techniques and a comparison with previously published data of related metabolites. Compound 2 was found to possess the first identified saturated internal C4-O-C14 linkage six-membered ring among all cembrane-type diterpenoids. The anti-proliferative activity of all the isolates (except 3) was evaluated against a limited panel of leukemia cell lines (Molt 4, K562, U937, and Sup-T1). The major compounds 8 and 10 exhibited the most anti-proliferative potent effect, with IC50 values ranging from 1.2 to 7.1 μM. The Structure Activity Relationship (SAR) of the isolates suggested that the presence of lactone moieties is crucial for the anti-proliferative activity against leukemia cells. Our work indicated that the development of an efficient aquaculture protocols for soft corals led to the discovery of new secondary metabolites with unique structural features. Such protocols can lead to a sustainable supply of biologically active compounds in enough quantities for the pharmaceutical industry. View Full-Text
Keywords: aquaculture Lobophytum crassum; cembranoids; Molt 4 leukemia; anti-proliferation; SAR aquaculture Lobophytum crassum; cembranoids; Molt 4 leukemia; anti-proliferation; SAR
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Peng, B.-R.; Lu, M.-C.; El-Shazly, M.; Wu, S.-L.; Lai, K.-H.; Su, J.-H. Aquaculture Soft Coral Lobophytum crassum as a Producer of Anti-Proliferative Cembranoids. Mar. Drugs 2018, 16, 15.

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