title: Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth.
abstract: Trypanosoma brucei parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide. Morinda lucida Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl3 fraction of M. lucida leaves, which possess activity against the GUTat 3.1 strain of T. brucei brucei The 50% inhibitory concentrations (IC50) of molucidin, ML-2-3, and ML-F52 were 1.27 μM, 3.75 μM, and 0.43 μM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of Trypanosoma parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Kofi D
authors.initials: KD
authors.lastname: Kwofie
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Nguyen Huu
authors.initials: NH
authors.lastname: Tung
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan mikkvip@tmd.ac.jp.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Suzuki-Ohashi
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Michael
authors.initials: M
authors.lastname: Amoa-Bosompem
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem, Ghana.
authors.forename: Richard
authors.initials: R
authors.lastname: Adegle
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem, Ghana.
authors.forename: Maxwell M
authors.initials: MM
authors.lastname: Sakyiamah
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem, Ghana.
authors.forename: Frederick
authors.initials: F
authors.lastname: Ayertey
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Kofi Baffour-Awuah
authors.initials: KB
authors.lastname: Owusu
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Isaac
authors.initials: I
authors.lastname: Tuffour
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Philip
authors.initials: P
authors.lastname: Atchoglo
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Kwadwo K
authors.initials: KK
authors.lastname: Frempong
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: William K
authors.initials: WK
authors.lastname: Anyan
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Morinaga
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem, Ghana.
authors.forename: Frederic
authors.initials: F
authors.lastname: Aboagye
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem, Ghana.
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Appiah
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Regina
authors.initials: R
authors.lastname: Appiah-Opong
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Nyarko
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem, Ghana.
authors.forename: Dominic
authors.initials: D
authors.lastname: Edoh
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Koram
authors.affiliation: Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Boakye
authors.affiliation: Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
authors.affiliation: Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
authors.forename: Irene
authors.initials: I
authors.lastname: Ayi
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology*; D032066:Morinda / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014345:Trypanosoma / Q000187:drug effects / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000503:physiopathology
chemical_list: D000981:Antiprotozoal Agents; D039823:Iridoids; D010936:Plant Extracts; D014344:Trypanocidal Agents