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
Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
Antimicrob Agents Chemother. 2016 May 23;60(6):3283-90. doi: 10.1128/AAC.01916-15. Print 2016 Jun.
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.
布氏锥虫寄生虫是动质体原生动物，通过人类非洲锥虫病（HAT）危害非洲数百万人的健康和经济福祉。由于目前药物存在严重的副作用和耐药性问题，人们一直急切期待新的化疗方法。最近，全球都在强调使用药用植物。亮叶巴戟是一种广泛分布于非洲的常见药用植物，几个研究小组已报道了该植物的抗原生动物活性。在本研究中，我们从亮叶巴戟叶的CHCl3组分中鉴定出三种新型四环环烯醚萜，莫卢西丁、ML-2-3和ML-F52，它们对布氏布氏锥虫的GUTat 3.1菌株具有活性。莫卢西丁、ML-2-3和ML-F52的50%抑制浓度（IC50）分别为1.27 μM、3.75 μM和0.43 μM。ML-2-3和ML-F52抑制副鞭毛杆蛋白亚基2（PFR-2）的表达，并导致细胞周期改变，这先于锥虫寄生虫血流形式的凋亡诱导。新型四环环烯醚萜可能是开发用于治疗人类和动物非洲锥虫感染的新化疗药物的有前景的先导化合物。
