TY - JOUR
T1 - New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth.
AU - Suzuki, Mitsuko
AU - Tung, Nguyen Huu
AU - Kwofie, Kofi D.
AU - Adegle, Richard
AU - Amoa-Bosompem, Michael
AU - Sakyiamah, Maxwell
AU - Ayertey, Frederick
AU - Owusu, Kofi Baffour Awuah
AU - Tuffour, Isaac
AU - Atchoglo, Philip
AU - Frempong, Kwadwo Kyereme
AU - Anyan, William K.
AU - Uto, Takuhiro
AU - Morinaga, Osamu
AU - Yamashita, Taizo
AU - Aboagye, Frederic
AU - Appiah, Alfred Ampomah
AU - Appiah-Opong, Regina
AU - Nyarko, Alexander K.
AU - Yamaoka, Shoji
AU - Yamaguchi, Yasuchika
AU - Edoh, Dominic
AU - Koram, Kwadwo
AU - Ohta, Nobuo
AU - Boakye, Daniel A.
AU - Ayi, Irene
AU - Shoyama, Yukihiro
N1 - Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/6/11
Y1 - 2015/6/11
N2 - 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 1H and 13C 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.
AB - 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 1H and 13C 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.
KW - Anti-trypanosomal activity
KW - Medicinal plants
KW - Molucidin
KW - Morinda lucida
KW - Tetracyclic iridoid
UR - http://www.scopus.com/inward/record.url?scp=84930924861&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2015.05.003
DO - 10.1016/j.bmcl.2015.05.003
M3 - Article
C2 - 26048790
AN - SCOPUS:84930924861
SN - 0960-894X
VL - 25
SP - 3030
EP - 3033
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 15
ER -
