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

作者：Suzuki Mitsuko; Tung Nguyen Huu; Kwofie Kofi D; Adegle Richard; Amoa Bosompem Michael; Sakyiamah Maxwell; Ayertey Frederick; Owusu Kofi Baffour Awuah; Tuffour Isaac; Atchoglo Philip; Frempong Kwadwo Kyereme; Anyan William K; Uto Takuhiro; Morinaga Osamu; Yamashita Taizo; Aboagye Frederic; Appiah Alfred Ampomah; Appiah Opong Regina; Nyarko Alexander K; Yamaoka Shoji; Yamaguchi Yasuchika; Edoh Dominic; Koram Kwadwo; Ohta Nobuo; Boakye Daniel A; Ayi Irene

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(15): 3030-3033.

DOI：10.1016/j.bmcl.2015.05.003

• Morinda lucida
• Tetracyclic iridoid
• Molucidin
• Anti-trypanosomal activity
• Medicinal plants

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 H-1 and C-13 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 mu M. 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.

• 出版日期2015-8-1
• 单位河北医科大学