483-15-8Relevant articles and documents
Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells
Benedetti, Serena,De Crescentini, Lucia,Mantellini, Fabio,Mari, Giacomo,Palma, Francesco,Santeusanio, Stefania
, p. 1606 - 1616 (2020)
Dihydroberberine (DHBER), the partially reduced form of the alkaloid berberine (BER), is known to exhibit important biological activities. Despite this fact, there have been only few studies that concern the biological properties of functionalized DHBER.
A new fluorescent probe for sensing of biothiols and screening of acetylcholinesterase inhibitors
Deng, Tao,Hu, Shiyou,Huang, Xin-An,Li, Yuge,Ling, Yanwu,Liu, Fang,Peng, Guiyuan,Wang, Xiaojuan,Wu, Shengjun
, p. 2468 - 2474 (2020)
A new N2O-type BODIPY probe (LF-Bop) has been proposed for the selective and sensitive detection of biologically relevant small molecular thiols. This detection is based on the Michael addition reaction between the thiol and nitrostyrene groups in the probe, which decreases the quenching effect from the nitro group, thus resulting in the recovery of the deep-red fluorescence from the BODIPY structure. The results show that LF-Bop is able to detect all tested free thiols through a fluorescence turn-on assay. The lowest limit of detection (LOD) for glutathione was found to be down to nanomolar levels (220 nM). Based on this probe, we have developed a new fluorescence assay for the screening of acetylcholinesterase inhibitors. In total, 11 natural and synthetic alkaloids have been evaluated. Both experimental measurements and theoretical molecular docking results reveal that both natural berberine and its synthetic derivative dihydroberberine are potential inhibitors of acetylcholinesterase.
Synthesis and structure of dihydroberberine nitroaryl derivatives – Potential ligands for G-quadruplexes
Burov, Oleg N.,Kurbatov, Sergey V.,Kletskii, Mikhail E.,Zagrebaev, Alexander D.,Mikhailov, Igor E.
, p. 335 - 340 (2017)
(Figure Presented) A method was developed for the synthesis of dihydroberberine nitroaryl derivatives on the basis of dihydroberberine reactions with aromatic electrophiles (picryl chloride, 4-chloro-7-nitrobenzofurazan, 4-chloro-5,7-dinitrobenzofurazan, and 7-chloro-4,6-dinitrobenzofuroxan). The obtained 13-substituted dihydroberberine derivatives represent structures with significant intramolecular charge transfer and, according to the results of molecular docking analysis, can effectively bind with G-quadruplexes of telomeric DNA fragments.
Visualizing semipermeability of the cell membrane using a pH-responsive ratiometric AIEgen
Gu, Yuan,Kwok, Ryan T. K.,Lam, Jacky W. Y.,Niu, Guangle,Tang, Ben Zhong,Wang, Yiming,Zhang, Han,Zhao, Zheng
, p. 5753 - 5758 (2020)
In clinical chemotherapy, some basic drugs cannot enter the hydrophobic cell membrane because of ionization in the acidic tumor microenvironment, a phenomenon known as ion trapping. In this study, we developed a method to visualize this ion trapping phenomenon by utilizing a pH-responsive ratiometric AIEgen, dihydro berberine (dhBBR). By observing the intracellular fluorescence ofdhBBR, we found that non-ionizeddhBBRcan enter cells more easily than ionized forms, which is in accordance with the concept of ion trapping. In addition,dhBBRshows superior anti-photobleaching ability toCurcuminthanks to its AIE properties. These results suggest thatdhBBRcan serve as a bioprobe for ion trapping.
Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes
Ferraroni, Marta,Bazzicalupi, Carla,Papi, Francesco,Fiorillo, Gaetano,Guamán-Ortiz, Luis Miguel,Nocentini, Alessio,Scovassi, Anna Ivana,Lombardi, Paolo,Gratteri, Paola
, p. 1107 - 1115 (2016)
The interaction between 13-phenylalkyl and 13-diphenylalkyl berberine derivatives (NAX) and human telomeric DNA G4 structures has been investigated by both spectroscopic and crystallographic methods. NAX042 and NAX053 are the best compounds improving the performance of the natural precursor berberine. This finding is in agreement with the X-ray diffraction result for the NAX053-Tel12 adduct, showing the ligand which interacts via π-stacking, sandwiched at the interface of two symmetry-related quadruplex units, with its benzhydryl group contributing to the overall stability of the adduct by means of additional π-stacking interactions with the DNA residues. The berberine derivatives were also investigated for their cytotoxic activity towards a panel of human cancer cell lines. Compounds NAX042 and NAX053 affect the viability of cancer cell lines in a dose-dependent manner.
Synthesis and anticancer activity of novel 9,13-disubstituted berberine derivatives
Wang, Zhi-Cheng,Wang, Jing,Chen, Huang,Tang, Jie,Bian, Ai-Wu,Liu, Ting,Yu, Li-Fang,Yi, Zhengfang,Yang, Fan
, (2020)
Novel berberine derivatives with disubstituents on positions C9 and C13 were synthesized and evaluated for antiproliferative activities against human prostate cancer cell lines (PC3 and DU145), breast cancer cell line (MDA-MB-231) and human colon cancer cell lines (HT29 and HCT116). All compounds showed significantly enhanced antiproliferative activities compared with berberine. Notably, compound 18e exhibited the strongest cytotoxicity against PC3 cells with an IC50 value of 0.19 μM, and the highest selectivity index (SIPC3 > 20). Further studies showed that 18e could arrest the cell cycle at G1 phase, and significantly inhibit tumor cell colony forming and migration even at low concentrations. Interestingly, 18e could significantly induce cytoplasmic vacuolation, suggesting a different mode of action from berberine.
Total Synthesis of (-)-Canadine, (-)-Rotundine, (-)-Sinactine, and (-)-Xylopinine Using a Last-Step Enantioselective Ir-Catalyzed Hydrogenation
Chen, Fener,Chen, Wenchang,Chen, Yu,Jiang, Meifen,Li, Weijian,Tang, Pei,Yang, Zhi
, p. 8143 - 8153 (2021/06/28)
A concise asymmetric total synthesis of a group of tetrahydroprotoberberine alkaloids, (-)-canadine, (-)-rotundine, (-)-sinactine, and (-)-xylopinine, has been accomplished in three steps from the commercially available corresponding disubstituted phenylethylamine and disubstituted benzaldehyde. Our synthesis toward these four alkaloids took advantage of the following strategy: In the first step, we achieved an efficient and sustainable synthesis of secondary amine hydrochlorides via a fully continuous flow; in the second step, we developed a Pictet-Spengler reaction/Friedel-Crafts hydroxyalkylation/dehydration cascade for the construction of the dihydroprotoberberine core structure (ABCD-ring); and in the last step, Ir-catalyzed enantioselective hydrogenation was employed for the introduction of the desired stereochemistry at the C-14 position in the tetrahydroprotoberberine alkaloids. This work significantly expedites the asymmetric synthesis of the entire tetrahydroprotoberberine alkaloid family as well as a more diverse set of structurally related non-natural analogues.
Discovery of C-9 modified berberine derivatives as novel lipid-lowering agents
Li, Dong-Dong,Yu, Pan,Xu, Hui,Wang, Zhen-Zhong,Xiao, Wei,Zhao, Lin-Guo
, p. 59 - 66 (2021/01/06)
Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.