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Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth

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 plagu... Full description

Journal Title: Antimicrobial agents and chemotherapy June 2016, Vol.60(6), pp.3283-90
Main Author: Kwofie, Kofi D
Other Authors: Tung, Nguyen Huu , Suzuki-Ohashi, Mitsuko , Amoa-Bosompem, Michael , Adegle, Richard , Sakyiamah, Maxwell M , Ayertey, Frederick , Owusu, Kofi Baffour-Awuah , Tuffour, Isaac , Atchoglo, Philip , Frempong, Kwadwo K , Anyan, William K , Uto, Takuhiro , Morinaga, Osamu , Yamashita, Taizo , Aboagye, Frederic , Appiah, Alfred A , Appiah-Opong, Regina , Nyarko, Alexander K , Yamaguchi, Yasuchika , Edoh, Dominic , Koram, Kwadwo A , Yamaoka, Shoji , Boakye, Daniel A , Ohta, Nobuo , Shoyama, Yukihiro , Ayi, Irene
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1098-6596 ; PMID: 26953191 Version:1 ; DOI: 10.1128/AAC.01916-15
Link: http://pubmed.gov/26953191
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recordid: medline26953191
title: Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth
format: Article
creator:
  • Kwofie, Kofi D
  • Tung, Nguyen Huu
  • Suzuki-Ohashi, Mitsuko
  • Amoa-Bosompem, Michael
  • Adegle, Richard
  • Sakyiamah, Maxwell M
  • Ayertey, Frederick
  • Owusu, Kofi Baffour-Awuah
  • Tuffour, Isaac
  • Atchoglo, Philip
  • Frempong, Kwadwo K
  • Anyan, William K
  • Uto, Takuhiro
  • Morinaga, Osamu
  • Yamashita, Taizo
  • Aboagye, Frederic
  • Appiah, Alfred A
  • Appiah-Opong, Regina
  • Nyarko, Alexander K
  • Yamaguchi, Yasuchika
  • Edoh, Dominic
  • Koram, Kwadwo A
  • Yamaoka, Shoji
  • Boakye, Daniel A
  • Ohta, Nobuo
  • Shoyama, Yukihiro
  • Ayi, Irene
subjects:
  • Antiprotozoal Agents -- Pharmacology
  • Iridoids -- Pharmacology
  • Morinda -- Chemistry
  • Plants, Medicinal -- Chemistry
  • Trypanocidal Agents -- Pharmacology
ispartof: Antimicrobial agents and chemotherapy, June 2016, Vol.60(6), pp.3283-90
description: 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.
language: eng
source:
identifier: E-ISSN: 1098-6596 ; PMID: 26953191 Version:1 ; DOI: 10.1128/AAC.01916-15
fulltext: fulltext
issn:
  • 10986596
  • 1098-6596
url: Link


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titleAntitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth
creatorKwofie, Kofi D ; Tung, Nguyen Huu ; Suzuki-Ohashi, Mitsuko ; Amoa-Bosompem, Michael ; Adegle, Richard ; Sakyiamah, Maxwell M ; Ayertey, Frederick ; Owusu, Kofi Baffour-Awuah ; Tuffour, Isaac ; Atchoglo, Philip ; Frempong, Kwadwo K ; Anyan, William K ; Uto, Takuhiro ; Morinaga, Osamu ; Yamashita, Taizo ; Aboagye, Frederic ; Appiah, Alfred A ; Appiah-Opong, Regina ; Nyarko, Alexander K ; Yamaguchi, Yasuchika ; Edoh, Dominic ; Koram, Kwadwo A ; Yamaoka, Shoji ; Boakye, Daniel A ; Ohta, Nobuo ; Shoyama, Yukihiro ; Ayi, Irene
ispartofAntimicrobial agents and chemotherapy, June 2016, Vol.60(6), pp.3283-90
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subjectAntiprotozoal Agents -- Pharmacology ; Iridoids -- Pharmacology ; Morinda -- Chemistry ; Plants, Medicinal -- Chemistry ; Trypanocidal Agents -- Pharmacology
descriptionTrypanosoma 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.
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titleAntitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth
descriptionTrypanosoma 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.
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authorKwofie, Kofi D ; Tung, Nguyen Huu ; Suzuki-Ohashi, Mitsuko ; Amoa-Bosompem, Michael ; Adegle, Richard ; Sakyiamah, Maxwell M ; Ayertey, Frederick ; Owusu, Kofi Baffour-Awuah ; Tuffour, Isaac ; Atchoglo, Philip ; Frempong, Kwadwo K ; Anyan, William K ; Uto, Takuhiro ; Morinaga, Osamu ; Yamashita, Taizo ; Aboagye, Frederic ; Appiah, Alfred A ; Appiah-Opong, Regina ; Nyarko, Alexander K ; Yamaguchi, Yasuchika ; Edoh, Dominic ; Koram, Kwadwo A ; Yamaoka, Shoji ; Boakye, Daniel A ; Ohta, Nobuo ; Shoyama, Yukihiro ; Ayi, Irene
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21Koram, Kwadwo A
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abstractTrypanosoma 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.
doi10.1128/AAC.01916-15
pmid26953191
issn00664804
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date2016-06