New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth.

Autor: Suzuki M; 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., Tung NH; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan., Kwofie KD; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Adegle R; Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana., Amoa-Bosompem M; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Sakyiamah M; Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana., Ayertey F; Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana., Owusu KB; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Tuffour I; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Atchoglo P; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Frempong KK; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Anyan WK; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Uto T; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan., Morinaga O; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan., Yamashita T; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan., Aboagye F; Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana., Appiah AA; Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana., Appiah-Opong R; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Nyarko AK; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Yamaoka S; Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Yamaguchi Y; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan., Edoh D; Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana., Koram K; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Ohta N; Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Boakye DA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Ayi I; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon LG 581, Ghana., Shoyama Y; Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan. Electronic address: shoyama@niu.ac.jp.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Aug 01; Vol. 25 (15), pp. 3030-3. Date of Electronic Publication: 2015 May 13.
DOI: 10.1016/j.bmcl.2015.05.003
Abstrakt: 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.
(Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: