Antitrypanosomal activities and mechanisms of action of novel tetracyclic iridoids from Morinda lucida Benth

Kofi D. Kwofie, Nguyen Huu Tung, Mitsuko Suzuki-Ohashi, Michael Amoa-Bosompem, Richard Adegle, Maxwell M. Sakyiamah, Frederick Ayertey, Kofi Baffour Awuah Owusu, Isaac Tuffour, Philip Atchoglo, Kwadwo K. Frempong, William K. Anyan, Takuhiro Uto, Osamu Morinaga, Taizo Yamashita, Frederic Aboagye, Alfred A. Appiah, Regina Appiah-Opong, Alexander K. Nyarko, Yasuchika YamaguchiDominic Edoh, Kwadwo A. Koram, Shoji Yamaoka, Daniel A. Boakye, Nobuo Ohta, Yukihiro Shoyama, Irene Ayi

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3283-3290
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number6
DOIs
Publication statusPublished - Jun 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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