Design and synthesis of new lupeol derivatives and their α-glucosidase inhibitory and cytotoxic activities

Abstract

A series of lupeol derivatives 2, 2a-2f, 2a-2h, 3a-3e, and 4a-4b were designed, synthesized and evaluated for their α-glucosidase inhibitory and cytotoxic activities. Among synthetic derivatives, lupeol analogues 2b and 2e containing a benzylidene chain exhibited the best activity against α-glucosidase and superior to the positive agent with the IC 50 values of 29.4 ± 1.33 and 20.1 ± 0.91 μM, respectively. Lupeol analogues 2d and 3a showed weak cytotoxicity against K562 cell line with the IC 50 values of 76.6 ± 2.40 and 94.4 ± 1.51 μM, respectively.

New Derivatives of Lupeol and Their Biological Activity

“…Isolated yield: 74.6 mg (37%), white solid. 1 H and 13 C NMR data were consistent with those reported previously [6].…”

“…Lupeol was isolated from the Vietnamese plant Bombax ceiba, following our previously reported procedure [8]. Lupeol was transformed to products 2, 2a, and 2b using oxidation with Oxone ® , a potassium triple-salt (KHSO 5 •1/2KHSO 4 •1/2K 2 SO 4 ) [6,9]. The conditions followed our previously reported method [6], with slight modifications.…”

“…Lupeol was transformed to products 2, 2a, and 2b using oxidation with Oxone ® , a potassium triple-salt (KHSO 5 •1/2KHSO 4 •1/2K 2 SO 4 ) [6,9]. The conditions followed our previously reported method [6], with slight modifications. Both 2a and 2b had the same molecular formula as C 32 H 52 O 4 .…”

“…Notably, lupeol has been reported to selectively target diseased and unhealthy human cells, while sparing normal and healthy cells [4]. Dozens of novel lupeol derivatives were synthesized and screened for their in vivo antihyperglycemic activity [5,6]. Most derivatives lowered the blood glucose levels, in a sucrose-challenged streptozotocin-induced diabetic rat (STZ-S) model [5].…”

“…Most derivatives lowered the blood glucose levels, in a sucrose-challenged streptozotocin-induced diabetic rat (STZ-S) model [5]. To continue our ongoing search for highly efficient antidiabetic agents from derivatized lupeol [6,7], we herein describe the synthesis of lupeol derivatives 2, 2a, 2b, and 3 (Figure 1). The structures of all the obtained compounds were characterized by 1 H, 13 C NMR, and HRESIMS.…”