title: Anti-Protozoal Activities of Cembrane-Type Diterpenes from Vietnamese Soft Corals.
abstract: Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an in vitro screening for anti-protozoal activity against Trypanosoma brucei rhodesiense (Tbr), T. cruzi (Tc), Leishmania donovani (Ld), and Plasmodium falciparum (Pf). Twelve of the tested compounds displayed significant activity against at least one of the parasites. Specifically, 7S,8S-epoxy-1,3,11-cembratriene-16-oic methyl ester (1), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (2), crassumol D (12), crassumol E (13), and (1S,2E,4S,6E,8S,11S)-2,6,12(20)-cembrantriene-4,8,11-triol (16) from Lobophytum crassum, L. laevigatum, and Sinularia maxima showed the highest level of inhibitory activity against T. b. rhodesiense, with IC50 values of about 1 µM or less. Lobocrasol A (6) and lobocrasol C (8) from L. crassum and L. laevigatum exhibited particularly significant inhibitory effects on L. donovani with IC50 values < 0.2 µM. The best antiplasmodial effect was exerted by laevigatol A (10), with an IC50 value of about 3.0 µM. The cytotoxicity of the active compounds on L6 rat skeletal myoblast cell was also assessed and found to be insignificant in all cases. This is the first report on anti-protozoal activity of these compounds, and points out the potential of the soft corals in discovery of new anti-protozoal lead compounds.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. thaonp@imbc.vast.vn.|Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18-Hoang Quoc Viet, Caugiay, Hanoi 10000, Vietnam. thaonp@imbc.vast.vn.
authors.forename: Nguyen Phuong
authors.initials: NP
authors.lastname: Thao
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. luyenbthoaduoc@gmail.com.
authors.forename: Bui Thi Thuy
authors.initials: BT
authors.lastname: Luyen
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstrasse 57, Basel CH-4002, Switzerland. reto.brun@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. reto.brun@unibas.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Swiss Tropical and Public Health Institute (Swiss TPH), Socinstrasse 57, Basel CH-4002, Switzerland. marcel.kaiser@unibas.ch.|University of Basel, Petersplatz 1, Basel CH-4003, Switzerland. marcel.kaiser@unibas.ch.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18-Hoang Quoc Viet, Caugiay, Hanoi 10000, Vietnam. phankiem@yahoo.com.
authors.forename: Phan
authors.initials: P
authors.lastname: Van Kiem
authors.affiliation: Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18-Hoang Quoc Viet, Caugiay, Hanoi 10000, Vietnam. cvminh@vast.vn.
authors.forename: Chau
authors.initials: C
authors.lastname: Van Minh
authors.affiliation: Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus, Corrensstrasse 48, Münster D-48149, Germany. thomschm@uni-muenster.de.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. kangjss@cnu.ac.kr.
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea. yhk@cnu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects; D010140:Pacific Ocean; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D051381:Rats; D013329:Structure-Activity Relationship; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects* / Q000254:growth & development; D014744:Vietnam
chemical_list: D000981:Antiprotozoal Agents; D004224:Diterpenes
keywords: Leishmania donovani; Plasmodium falciparum; Trypanosoma brucei; anti-protozoal activity; cembrane-type diterpenes; marine natural product; neglected tropical diseases; soft coral