Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter.
Three new picraline-type alkaloids, alstiphyllanines E-G (1-3) and a new ajmaline-type alkaloid, alstiphyllanine H (4) were isolated from the leaves of Alstonia macrophylla together with 16 related alkaloids (5-20). Structures and stereochemistry of 1-4 were fully elucidated and characterized by 2D NMR analysis. Alstiphyllanines E and F (1 and 2) showed moderate Na(+)-glucose cotransporter (SGLT1 and SGLT2) inhibitory activity. A series of a hydroxy substituted derivatives 21-28 at C-17 of the picraline-type alkaloids have been derived as having potent SGLT inhibitory activity. 10-Methoxy-N(1)-methylburnamine-17-O-veratrate (6) exhibited potent inhibitory activity, suggesting that the presence of an ester side chain at C-17 may be important to show SGLT inhibitory activity. Structure activity relationship of alstiphyllanines on inhibitory activity of SGLT was discussed.
Arai
Hiroko
H
Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan.
Hirasawa
Yusuke
Y
Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan.
Rahman
Abdul
A
Faculty of Pharmacy, Airlangga University, Jalan Dharmawangsa Dalam, Surabaya 60286, Indonesia.
Kusumawati
Idha
I
Faculty of Pharmacy, Airlangga University, Jalan Dharmawangsa Dalam, Surabaya 60286, Indonesia.
Zaini
Noor Cholies
NC
Faculty of Pharmacy, Airlangga University, Jalan Dharmawangsa Dalam, Surabaya 60286, Indonesia.
Sato
Seizo
S
Central Research Laboratory, Nippon Suisan Kaisha, Ltd, 559-6 Kitano-machi, Hachioji, Tokyo 192-0906, Japan.
Aoyama
Chihiro
C
Central Research Laboratory, Nippon Suisan Kaisha, Ltd, 559-6 Kitano-machi, Hachioji, Tokyo 192-0906, Japan.
Takeo
Jiro
J
Central Research Laboratory, Nippon Suisan Kaisha, Ltd, 559-6 Kitano-machi, Hachioji, Tokyo 192-0906, Japan.
Morita
Hiroshi
H
Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan.
D031051:Alstonia / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008968:Molecular Conformation; D018515:Plant Leaves / Q000737:chemistry*; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors*; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D026121:Indole Alkaloids; D051269:Sodium-Glucose Transporter 1; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C549690:alstiphyllanine E; C549689:alstiphyllanine H