3606-45-9Relevant academic research and scientific papers
Re-engineering and synthesis of cytotoxic 2,3:7,8-di(alkylenedioxy)-extended analogs of quaternary sanguinarine chloride
Li, Qi-Lin,Deng, An-Jun,Ji, Ming,Li, Zhi-Hong,Chen, Xiao-Guang,Qin, Hai-Lin
, p. 1137 - 1153 (2018)
A method was developed to synthesize 2,3:7,8-di(alkylenedioxy)-extended analogs of quaternary sanguinarine chloride. 1-Bromo-2-bromomethyl-3,4-alkylenedioxy benzenes and 6,7-alkylenedioxynaphthalen-1-amines were synthesized first. Reactions to construct the target compounds with these two series of synthons involved alterations on a published method for synthesizing 2,3,7,8-tetraoxygenated derivatives of benzo[c]phenanthridinium, substituting benzyl bromides for benzoic aldehydes, prolonging the radical annulation time, and conducting N-methylation with formic acid and NaBH4. All the target compounds showed the same or better in vitro growth inhibitory activities against cancer cell lines compared with the positive compound. The structure activity relationship relevant to cytotoxicity and lipophilicity of the target compounds was produced.
The synthesis and biological evaluation of sanguinarine derivatives as anti-non-small cell lung cancer agents
Ding, Ke,Jiang, Liang,Lu, Xiaoyun,Wang, Xiaolu,Wang, Yuting,Xu, Fang,Zhang, Zhang
, p. 293 - 296 (2020)
A novel series of sanguinarine (SA) derivatives were synthesized and evaluated as anti-non-small cell lung cancer (NSCLC) agents. The compounds inhibited A549 and H1975 NSCLC cells with IC50 values of 0.96->30 ΜM and 0.79->30 ΜM, respectively. Compounds 8d-8j exhibited low micromolar inhibitory activity and indicated that the C6-position of SA was tolerated to be substituted by hydrophilic groups and CN. Further investigation of their mechanism of action showed that compound 8h induced apoptosis of A549 and H1975 cells by inhibiting the Akt signaling pathway and elevating the reactive oxygen species (ROS). This study provided a strategy for developing new anti-cancer agents.
Fluorescence of sanguinarine: Spectral changes on interaction with amino acids
Janovska, Marika,Kubala, Martin,Simanek, Vilim,Ulrichova, Jitka
, p. 11335 - 11341 (2010)
The quaternary isoquinoline alkaloid, sanguinarine (SG) exhibits a wide range of biological activities. This study examines spectral changes expected from SG binding to proteins. Fluorescence spectra of the cationic form of sanguinarine (SG+) are sensitive to environment polarity. On the other hand, spectra of the neutral form of sanguinarine, pseudobase (SGOH) and dihydrosanguinarine (DHSG, the first metabolite of SG) exhibit higher sensitivity to the ability of solvent to form a solute-to-solvent hydrogen bonds. Interaction with cysteine has been the only mode of SG binding to enzymes that has been considered so far. In reality, our experiments have revealed spectral changes on specific interactions of SG+ with Cys, Glu and Tyr in the protic environment and with Arg and Glu in the aprotic environment. We have also detected interactions of SGOH with Cys in the protic environment and with Cys, Glu and Lys in the aprotic environment. The DHSG spectra were only altered in the presence of the Cys analog in the protic environment. We have also demonstrated that spectral change analysis can aid investigation of SG/DHSG interactions with proteins and we were able to identify SG+-binding site on Na+/K+-ATPase.
FORMATION OF ALKALOIDS IN CORYDALIS OPHIOCARPA CALLUS CULTURE
Iwasa, K.,Takao, N.
, p. 611 - 614 (1982)
Corydalis ophiocarpa callus tissue was examined for its isoquinoline alkaloid content.The culture has good biosynthetic capabilities for transformation of exogenous alkaloids.Key Word Index - Corydalis ophiocarpa; Papaveraceae; callus tissue; biotransformation; isoquinoline alkaloids.
The toxicity and pharmacokinetics of dihydrosanguinarine in rat: A pilot study
Vrublova, Eva,Vostalova, Jitka,Vecera, Rostislav,Klejdus, Borivoj,Stejskal, David,Kosina, Pavel,Zdarilova, Adela,Svobodova, Alena,Lichnovsky, Vaclav,Anzenbacher, Pavel,Dvorak, Zdenek,Vicar, Jaroslav,Simanek, Vilim,Ulrichova, Jitka
, p. 2546 - 2553 (2008)
The quaternary benzo[c]phenanthridine alkaloid sanguinarine (SG) is the main component of Sangrovit, a natural livestock feed additive. Dihydrosanguinarine (DHSG) has recently been identified as a SG metabolite in rat. The conversion of SG to DHSG is a likely elimination pathway of SG in mammals. This study was conducted to evaluate the toxicity of DHSG in male Wistar rats at concentrations of 100 and 500 ppm DHSG in feed for 90 days (average doses of 14 and 58 mg DHSG/kg body weight/day). No significant alterations in body or organ weights, macroscopic details of organs, histopathology of liver, ileum, kidneys, tongue, heart or gingiva, clinical chemistry or hematology markers in blood in the DHSG-treated animals were found compared to controls. No lymphocyte DNA damage by Comet assay, formation of DNA adducts in liver by 32P-postlabeling, modulation of cytochrome P450 1A1/2 or changes in oxidative stress parameters were found. Thus, repeated dosing of DHSG for 90 days at up to 500 ppm in the diet (i.e. approximately 58 mg/kg/day) showed no evidence of toxicity in contrast to results published in the literature. In parallel, DHSG pharmacokinetics was studied in rat after oral doses 9.1 or 91 mg/kg body weight. The results showed that DHSG undergoes enterohepatic cycling with maximum concentration in plasma at the first or second hour following application. DHSG is cleared from the body relatively quickly (its plasma levels drop to zero after 12 or 18 h, respectively).
Visible-Light-Promoted Biomimetic Reductive Functionalization of Quaternary Benzophenanthridine Alkaloids
Wang, Lin,Wang, Xinhao,Wang, Wei,Liu, Wei,Liu, Yisong,Xie, Hongqi,Reiser, Oliver,Zeng, Jianguo,Cheng, Pi
supporting information, p. 2390 - 2397 (2021/08/20)
Reduction of an iminium C=N double bond is the most important phase I metabolism process associated with the cytotoxic property of quaternary benzophenanthridine alkaloids (QBAs). Inspired by the light-mediated reduction of QBAs with nicotinamide adenine dinucleotide, a visible-light-promoted reductive functionalization reaction of QBAs is reported in this study. C4-Alkyl-1,4-dihydropyridines (DHPs) enable the direct reductive alkylation of QBA independently, serving as both single-electron-transfer reductant reagents under irradiation with 455 nm blue light in the absence of photocatalysts and additional additives. Our protocol can be further applied to the semisynthesis of natural 6-substituted dihydrobenzophenanthridine derivatives such as O-acetyl maclekarpine E.
Oxidative dehydrogenation method and application of compound with cell nucleus-targeted light-activated imaging and cancer cell killing capabilities
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Paragraph 0072; 0078-0081, (2020/06/17)
The invention belongs to the technical field of medical materials, and discloses an oxidative dehydrogenation method and application of a compound with cell nucleus-targeted light-activated imaging and cancer cell killing capabilities. The method comprises a step of reacting dihydrobenzophenanthridine alkaloid with oxygen under an illumination condition to obtain benzophenanthridine alkaloid. Thestructure of the dihydrotriphenanthridine alkaloid is as shown in a formula I which is described in the specification. The invention also discloses application of the dihydrotriphenanthridine alkaloidin preparation of a cell nucleus-targeted light-activated imaging agent and/or a light-activated anti-tumor product. The oxidative dehydrogenation method is simple and efficient; the dihydrobenzophenanthridine alkaloid is used in cells, and illumination is carried out in the presence of oxygen, so specific light-activated fluorescence imaging targeted to cell nucleuses in living cells is achieved, and the method has the advantages of high light activation efficiency, high signal-to-noise ratio, small cytotoxicity, large Stokes shift, high in cell entering capacity and the like. Through illumination control, selective targeted light-activated fluorescence imaging of cell nucleuses in cancer cells and selective killing of the cancer cells are realized.
Sanguinarine is reduced by NADH through a covalent adduct
Sandor, Roman,Slanina, Jiri,Midlik, Adam,Sebrlova, Kristyna,Novotna, Lucie,Carnecka, Martina,Slaninova, Iva,Taborsky, Petr,Taborska, Eva,Pes, Ondrej
, p. 77 - 84 (2017/11/07)
Sanguinarine is a benzo[c]phenanthridine alkaloid with interesting cytotoxic properties, such as induction of oxidative DNA damage and very rapid apoptosis, which is not mediated by p53-dependent signaling. It has been previously documented that sanguinarine is reduced with NADH even in absence of any enzymes while being converted to its dihydro form. We found that the dark blue fluorescent species, observed during sanguinarine reduction with NADH and misinterpreted by Matkar et al. (Arch. Biochem. Biophys. 2008, 477, 43–52) as an anionic form of the alkaloid, is a covalent adduct formed by the interaction of NADH and sanguinarine. The covalent adduct is then converted slowly to the products, dihydrosanguinarine and NAD+, in the second step of reduction. The product of the reduction, dihydrosanguinarine, was continually re-oxidized by the atmospheric oxygen back to sanguinarine, resulting in further reacting with NADH and eventually depleting all NADH molecules. The ability of sanguinarine to diminish the pool of NADH and NADPH is further considered when explaining the sanguinarine-induced apoptosis in living cells.
New methods for the synthesis of naphthyl amines; Application to the synthesis of dihydrosanguinarine, sanguinarine, oxysanguinarine and (±)-maclekarpines B and C
Tatton, Matthew R.,Simpson, Iain,Donohoe, Timothy J.
, p. 11314 - 11316 (2014/11/07)
A new method for preparing naphthyl amines from 1,5 unsaturated dicarbonyl precursors is described; the utility of this new method was proven in the syntheses of several natural products, all containing the benzo[c]phenanthridine core and enabled by a radical promoted cyclisation of the naphthyl amine products formed in the key cyclisation. the Partner Organisations 2014.
Isolation and characterization of a cDNA encoding (S)-cis-N-methylstylopine 14-hydroxylase from opium poppy, a key enzyme in sanguinarine biosynthesis
Beaudoin, Guillaume A.W.,Facchini, Peter J.
, p. 597 - 603 (2013/05/08)
Sanguinarine is a benzo[. c]phenenthridine alkaloid with potent antimicrobial properties found commonly in plants of the Papaveraceae, including the roots of opium poppy (. Papaver somniferum). Sanguinarine is formed from the central 1-benzylisoquinoline intermediate (. S)-reticuline via the protoberberine alkaloid (. S)-scoulerine, which undergoes five enzymatic oxidations and an N-methylation. The first four oxidations from (. S)-scoulerine are catalyzed by cytochromes P450, whereas the final conversion involves a flavoprotein oxidase. All but one gene in the biosynthetic pathway from (. S)-reticuline to sanguinarine has been identified. In this communication, we report the isolation and characterization of (. S)-. cis-. N-methylstylopine 14-hydroxylase (MSH) from opium poppy based on the transcriptional induction in elicitor-treated cell suspension cultures and root-specific expression of the corresponding gene. Along with protopine 6-hydroxylase, which catalyzes the subsequent and penultimate step in sanguinarine biosynthesis, MSH is a member of the CYP82N subfamily of cytochromes P450. The full-length MSH cDNA was expressed in Saccharomyces cerevisiae and the recombinant microsomal protein was tested for enzymatic activity using 25 benzylisoquinoline alkaloids representing a wide range of structural subgroups. The only enzymatic substrates were the N-methylated protoberberine alkaloids N-methylstylopine and N-methylcanadine, which were converted to protopine and allocryptopine, respectively.
