title: New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth.
abstract: Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious health problem in many African countries with thousands of new infected cases annually. Chemotherapy, which is the main form of control against HAT has been characterized lately by the viewpoints of toxicity and drug resistance issues. Recently, there have been a lot of emphases on the use of medicinal plants world-wide. Morinda lucida Benth. is one of the most popular medicinal plants widely distributed in Africa and several groups have reported on its anti-protozoa activities. In this study, we have isolated one novel tetracyclic iridoid, named as molucidin, from the CHCl3 fraction of the M. lucida leaves by bioassay-guided fractionation and purification. Molucidin was structurally elucidated by (1)H and (13)C NMR including HMQC, HMBC, H-H COSY and NOESY resulting in tetracyclic iridoid skeleton, and its absolute configuration was determined. We have further demonstrated that molucidin presented a strong anti-trypanosomal activity, indicating an IC50 value of 1.27 μM. The cytotoxicity study using human normal and cancer cell lines indicated that molucidin exhibited selectivity index (SI) against two normal fibroblasts greater than 4.73. Furthermore, structure-activity relationship (SAR) study was undertaken with molucidin and oregonin, which is identical to anti-trypanosomal active components of Alnus japonica. Overlapping analysis of the lowest energy conformation of molucidin with oregonin suggested a certain similarities of aromatic rings of both oregonin and molucidin. These results contribute to the future drug design studies for HAT.
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana; Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Nguyen Huu
authors.initials: NH
authors.lastname: Tung
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Kofi D
authors.initials: KD
authors.lastname: Kwofie
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Richard
authors.initials: R
authors.lastname: Adegle
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Michael
authors.initials: M
authors.lastname: Amoa-Bosompem
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Sakyiamah
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Frederick
authors.initials: F
authors.lastname: Ayertey
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Kofi Baffour-Awuah
authors.initials: KB
authors.lastname: Owusu
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Isaac
authors.initials: I
authors.lastname: Tuffour
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Philip
authors.initials: P
authors.lastname: Atchoglo
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Kwadwo Kyereme
authors.initials: KK
authors.lastname: Frempong
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: William K
authors.initials: WK
authors.lastname: Anyan
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Morinaga
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Frederic
authors.initials: F
authors.lastname: Aboagye
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Alfred Ampomah
authors.initials: AA
authors.lastname: Appiah
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Regina
authors.initials: R
authors.lastname: Appiah-Opong
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Nyarko
authors.affiliation: Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Dominic
authors.initials: D
authors.lastname: Edoh
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Kwadwo
authors.initials: K
authors.lastname: Koram
authors.affiliation: Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Boakye
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana.
authors.forename: Irene
authors.initials: I
authors.lastname: Ayi
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan. Electronic address: shoyama@niu.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D039823:Iridoids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008958:Models, Molecular; D032066:Morinda / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy
chemical_list: D039823:Iridoids; D010936:Plant Extracts; D014344:Trypanocidal Agents
keywords: Anti-trypanosomal activity; Medicinal plants; Molucidin; Morinda lucida; Tetracyclic iridoid