Optimization of Rutaecarpine as ABCA1 Up-Regulator for Treating Atherosclerosis

Abstract

ATP-binding cassette transporter A1 (ABCA1) is a key transporter and receptor in promoting cholesterol efflux, and increasing the expression level of ABCA1 is antiatherogenic. In our previous study, rutaecarpine (RUT) was found to protect ApoE(-/-) mice from developing atherosclerosis through preferentially up-regulating ABCA1 expression. In the present work, a series of RUT derivatives were synthesized and examined as ABCA1 expression up-regulators. Compounds CD1, CD6, and BCD1-2 were found to possess the most potential activity as antiatherosclerotic agents among all compounds tested.

Progress in Studies on Rutaecarpine. II.—Synthesis and Structure-Biological Activity Relationships

“…Recent years have witnessed steady progress in understanding the chemistry and biology of rutaecarpine. Furthermore, it should be noted that reports have been issued on the beneficial effects of rutaecarpine analogues on controlling lipid accumulation [52], obesity [53], and atherosclerosis [54,55], and. The present review focuses on the synthesis of rutaecarpine derivatives and on their biological activities, especially on structure-activity relationships and their antiplatelet, vasodilatory, cytotoxic, and anticholinesterase activities.…”

“…Recently, Xu et al . reported the anti-atherosclerosis activity (EC 50 = 0.27 μM) by up-regulating ATP-binding cassette transporter A1 (ABCA1) [54,55]. The present review addresses structure-activity relationships with respect to antiplatelet activity, vasodilator activity, cytotoxicity, and anticholinesterase activity.…”

Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

“…Rutaecarpine lowered the level of TC, TG, LDL-C, and hs-CRP in hyperlipidemic and hyperglycemic rats via AMPK activation and NF-kB inhibition (Nie et al, 2016;Tian et al, 2019b). Several derivatives of rutaecarpine also exhibited antiatherosclerotic potential by enhancing cholesterol efflux from RAW264.7 macrophages to HDL and thus inhibiting foam cell formation (Li et al, 2014).…”

Rational Design of a New Class of Toll-Like Receptor 4 (TLR4) Tryptamine Related Agonists by Means of the Structure- and Ligand-Based Virtual Screening for Vaccine Adjuvant Discovery

“…The compounds 14 – 25 were synthesized by two different procedures (A and B). In this work both previously synthesized tryptamine derivatives 14 – 20 [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ] and new tryptamine derivatives 21 – 25 have been prepared. Products 14 – 21 were prepared by nucleophilic acyl substitution of tryptamine ( 1 ) by the commercially available acyl chlorides 2 – 9 .…”