Benzophenanthridine Alkaloids (benzophenanthridine + alkaloid)

Distribution by Scientific Domains


Selected Abstracts


Formation of Human Telomeric G-quadruplex Structures Induced by the Quaternary Benzophenanthridine Alkaloids: Sanguinarine, Nitidine, and Chelerythrine

CHINESE JOURNAL OF CHEMISTRY, Issue 5 2010
Shu Yang
Abstract The ligands which can facilitate the formation and stabilize G-quadruplex structures have attracted enormous attention due to their potential ability of inhibiting the telomerase activity and halting tumor cell proliferation. It is noteworthy that the abilities of the quaternary benzophenanthridine alkaloids (QBAs), the very important G-quadruplex binders, in inducing the formation of human telomeric DNA G-quadruplex structures, have not been reported. Herein, the interaction between single-strand human telomeric DNA and three QBAs: Sanguinarine (San), Nitidine (Nit) and Chelerythrine (Che), has been investigated. Although these molecules are very similar in structure, they exhibit significantly different abilities in inducing oligonucleotide d(TTAGGG)4 (HT4) to specific G-quadruplex structures. Our experimental results indicated that the best ligand San could convert HT4 into antiparallel G-quadruplex structure completely, followed by Nit, which could transform to mixed-type or hybrid G-quadruplex structure partially, whereas Che could only transform to antiparallel G-quadruplex structure in small quantities. The relative QBAs' inducing abilities as indicated by the CD data are in the order of San>Nit>Che. Further investigation revealed that the G-quadruplex structures from HT4 induced by QBAs are of intramolecular motif. And only sequences with certain length could be induced by QBAs because of their positive charges which could not attract short chain DNA molecules to close to each other and form intermolecular G-quadruplex. In addition, the factors that affect the interaction between HT4 and QBAs were discussed. It is proposed that the thickness of the molecular frame and the steric hindrance are the primary reasons why the subtle differences in QBAs' structure lead to their remarkable differences in inducing the formation of the G-quadruplex structures. [source]


Protective Effect of Sanguinarine on Ultraviolet B-mediated Damages in SKH-1 Hairless Mouse Skin: Implications for Prevention of Skin Cancer

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2007
Haseeb Ahsan
Excessive exposure of solar ultraviolet (UV) radiation, particularly its UVB component (280,320 nm), to human skin is the major cause of skin cancers. UV exposure also leads to the development of precancerous conditions such as actinic keratosis and elicits a variety of other adverse effects such as sunburn, inflammation, hyperplasia, immunosuppression and skin aging. Therefore, there is a need to intensify our efforts towards the development of novel mechanism-based approaches/agents for the protection of UVB-mediated damages. Chemoprevention is being investigated as a potential approach for the management of UV damages including skin cancer. We have earlier shown that sanguinarine, a benzophenanthridine alkaloid, inhibits UVB exposure-mediated damages in HaCaT keratinocytes. In this study, to determine the relevance of our in vitro findings to in vivo situations, we assessed the effects of sanguinarine on UVB-mediated damages in SKH-1 hairless mice. Our data demonstrated that a topical application of sanguinarine (5 ,mol 0.3 mL,1 ethanol per mouse), either as a pretreatment (30 min prior to UVB) or posttreatment (5 min after UVB), resulted in a significant decrease in UVB-mediated increases in skin edema, skin hyperplasia and infiltration of leukocytes. Further, sanguinarine treatments (pre and post) also resulted in a significant decrease in UVB mediated (1) generation of H2O2 and (2) increases in the protein levels of markers of tumor promotion/proliferation viz. ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA) and Kiel antigen-67. Based on this data, we suggest that sanguinarine could be developed as an agent for the management of conditions elicited by UV exposure including skin cancer. However, further detailed studies are needed to support this suggestion. [source]


Argemone oil induced cellular damage in the reproductive tissues of transgenic Drosophila melanogaster: Protective role of 70 kDa heat shock protein

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2003
Indranil Mukhopadhyay
Abstract We explored the reproductive toxicity of argemone oil and its principal alkaloid fraction in transgenic Drosophila melanogaster (hsp70-lacZ) Bg9. The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Freshly eclosed first instar larvae of transgenic Drosophila melanogaster were transferred to different concentrations of argemone oil and its alkaloid fraction contaminated food. Virgin flies that eclosed from the contaminated food were pair-mated to look into the effect on reproduction. The study was further extended by investigating hsp70 expression and tissue damage in larval gonads, genital discs, and reproductive organs of adult fly. Our results showed that argemone oil was more cytotoxic than its principal alkaloid fraction. Moreover, it was the male fly that was more affected compared to its opposite number. The accessory glands of male reproductive system of the fly, which did not express hsp70, exhibited severe damage as evidenced by Trypan blue staining. This prompted us to explore the ultrastructural morphology of the gland, which showed acute signs of necrosis in both the cell types as evident by necrotic nuclei, higher vacuolization, and disorganized endoplasmic reticulum, decrease in the number of Golgi vesicles and disorganized, loosely packed filamentous structures in the lumen of the accessory gland, at the higher concentrations of the adulterant. The study showed the reproductive toxicity of argemone oil and its alkaloid fraction in transgenic Drosophila melanogaster and further confirmed the cytoprotective role of hsp70. 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:223,234, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10082. [source]


Analysis of secondary metabolites from eschscholtzia californica by high-performance liquid chromatography

PHYTOCHEMICAL ANALYSIS, Issue 4 2006
Maya Klvana
Abstract A rapid and precise analytical HPLC method has been developed for screening the major benzophenanthridine alkaloids produced by cell cultures of Eschscholtzia californica, namely, sanguinarine, chelirubine, macarpine, chelerythrine and chelilutine. Separation was achieved on a C18 reversed-phase column with gradient elution using acetonitrile and 50 mm phosphoric acid. Detection was performed by both fluorescence (,ex 330 nm, ,em 570 nm) and photodiode array, leading to good selectivity and precision in determining peak purity. A simple and quick sample preparation protocol was elaborated involving a methanolic extraction for the measurement of intracellular concentrations of the alkaloids and a solid phase extraction for their quantification in culture medium. Owing to the non-availability of commercially standards, a method for the purification of chelirubine, macarpine and chelilutine by semi-preparative HPLC was developed. Coupled together, the isolation method and the analytical method were highly reliable for screening the alkaloids of interest produced by E. californica. Copyright 2006 John Wiley & Sons, Ltd. [source]


Formation of Human Telomeric G-quadruplex Structures Induced by the Quaternary Benzophenanthridine Alkaloids: Sanguinarine, Nitidine, and Chelerythrine

CHINESE JOURNAL OF CHEMISTRY, Issue 5 2010
Shu Yang
Abstract The ligands which can facilitate the formation and stabilize G-quadruplex structures have attracted enormous attention due to their potential ability of inhibiting the telomerase activity and halting tumor cell proliferation. It is noteworthy that the abilities of the quaternary benzophenanthridine alkaloids (QBAs), the very important G-quadruplex binders, in inducing the formation of human telomeric DNA G-quadruplex structures, have not been reported. Herein, the interaction between single-strand human telomeric DNA and three QBAs: Sanguinarine (San), Nitidine (Nit) and Chelerythrine (Che), has been investigated. Although these molecules are very similar in structure, they exhibit significantly different abilities in inducing oligonucleotide d(TTAGGG)4 (HT4) to specific G-quadruplex structures. Our experimental results indicated that the best ligand San could convert HT4 into antiparallel G-quadruplex structure completely, followed by Nit, which could transform to mixed-type or hybrid G-quadruplex structure partially, whereas Che could only transform to antiparallel G-quadruplex structure in small quantities. The relative QBAs' inducing abilities as indicated by the CD data are in the order of San>Nit>Che. Further investigation revealed that the G-quadruplex structures from HT4 induced by QBAs are of intramolecular motif. And only sequences with certain length could be induced by QBAs because of their positive charges which could not attract short chain DNA molecules to close to each other and form intermolecular G-quadruplex. In addition, the factors that affect the interaction between HT4 and QBAs were discussed. It is proposed that the thickness of the molecular frame and the steric hindrance are the primary reasons why the subtle differences in QBAs' structure lead to their remarkable differences in inducing the formation of the G-quadruplex structures. [source]