A Series of β-Carboline Alkaloids from the Seeds of <i>Peganum harmala</i> Show G-Quadruplex Interactions

Wang, Kai Bo; Li, Da Hong; Hu, Ping; Wang, Wen Jing; Lin, Clement; Wang, Jian; Lin, Bin; Bai, Jiao; Pei, Yue Hu; Jing, Yong Kui; Li, Zhan Lin; Yang, Danzhou; Hua, Hui

doi:10.1021/acs.orglett.6b01560

Cited by 48 publications

(17 citation statements)

References 28 publications

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“…Our previous study revealed that alkaloids from M . cordata exhibited promising antiproliferative effects, so all the isolated compounds were tested for the growth inhibitory activities against HL-60, A-549, MCF-7 human cancer cell lines by the trypan blue method and MTT method 9 , 10 . The results were summarized in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

Sai¹,

Li²,

Li³

et al. 2017

Sci Rep

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(±)-Macleayins F-H (1-3), three pairs of new enantiomeric alkaloid dimers, along with four known alkaloids (4-7) as their plausible biogenetic precursors, were isolated from the aerial parts of Macleaya cordata. Compounds 1-3 were obtained under the guidance of LC-MS investigation, and their structures were elucidated by analysis of the 1D and 2D NMR spectroscopic data. The racemic mixtures were successfully separated by chiral HPLC, and the absolute configurations of enantiomers were determined by electronic circular dichroism (ECD) spectroscopy. Compounds 1-7 showed antiproliferative activity against HL-60 with IC 50 values of 1.34-41.30 μM, especially compounds 1-2 exhibited the best inhibitory activity against HL-60 cell lines. In addition, the preliminary mechanism investigation for compound 2 using Annexin V/7-AAD double-staining assay, DAPI staining assay and JC-1 staining method, indicated that 2 inhibited cancer cell proliferation potentially through inducing apoptosis via the mitochondria-related pathway and arrested cell cycle of HL-60 cells at S phase.Benzophenanthridine and protopine alkaloids occur in Macleaya cordata (Willd) R. Br. and have been investigated for their intriguing bioactivity, such as anticancer, anti-bacterial, insecticidal, and anti-inflammatory effects 1,2 . Macleaya cordata is a perennial plant in the family of Papaveraceae, which has been used in folk medicine for the treatment of cervical cancer, thyroid cancer, inflamed wounds, ringworm infection, arthritis, and trichomonas vaginalis 3,4 . In our previous investigation, two pairs of enantiomeric alkaloid dimers (macleayins A and B) with cytotoxicity were isolated from M. cordata 5 . In our present study, LC-MS-guided fractionation (Fig. 1) led to the isolation of three pairs of analogous dimers, macleayins F-H (1-3) biogenetically derived from a benzophenanthridine and protopine alkaloid through C6-C 13′ linkage. Four possible biogenetic precursors, sanguinarine, chelerythrine, protopine, and allocryptopine (4-7) were obtained (Fig. 2). Herein, we reported the isolation, and structural elucidation of new compounds. In addition, the antiproliferative properties and action mechanism were also investigated. Results and DiscussionStructural Elucidation of Compounds 1a/1b-3a/3b. Macleayin F (1) was isolated as white amorphous powder, with the molecular formula of C 41 H 36 N 2 O 9 , deduced from HRESIMS [M + H] + (m/z 701.2491, calcd for 701.2494), appropriate for 25 degrees of unsaturation. The IR spectrum indicated the presence of ketone carbonyl (1656 cm −1 ), methylenedioxyl group (2792, 941 cm −1 ), and aromatic ring (1616, 1486, 1462 cm −1 ). In the UV spectrum, the absorption maxima at 227 and 287 nm were detected. The HRESIMS/MS spectrum exhibited the

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Section: Resultsmentioning

confidence: 99%

LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

Sai¹,

Li²,

Li³

et al. 2017

Sci Rep

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“…β-carboline alkaloids lead to the formation of G-quadruplexes which consist of four guanine bases assembling in a three-dimensional square planar structure. These arrangements play regulatory roles on genes, most importantly on oncogenes, thus acting as antitumor agents against human promyelocytic leukemia, prostate cancer, and gastric cancer [ 46 , 78 , 79 ]. The formation of G-quadruplexes can be considered as a novel approach for cancer treatment and can have promising applications in anticancer drug design.…”

Section: Emerging Cytotoxic Alkaloids: Apoptotic Strategmentioning

confidence: 99%

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

et al. 2017

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Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery.

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“…Article Related Abbreviations: EIC, extracted ion chromatogram; FA, formic acid human cancer cell lines [6]. Four pairs of partially racemized beta-carboline alkaloids with rare carbon skeleton from Peganum harmala L. seeds showed the strongest Gquadruplex interaction and exhibited significant cytotoxic activity against three cancer cell lines [7]. Therefore, the purification and pharmacological study of different alkaloids especially trace alkaloids are of great significance.…”

Section: Introductionmentioning

confidence: 99%

A strategy for efficient enrichment of steroidal alkaloids from Fritillaria based on fluorinated reversed‐phase stationary phase

Zhou

et al. 2021

J of Separation Science

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Plant-derived alkaloids are bioactive natural ingredients, but their contents are relatively low in plants. Therefore, the efficient enrichment of alkaloids is a prerequisite for purification and further pharmacological research. In this study, an efficient and simple strategy for enrichment of steroidal alkaloids in Fritillaria was developed for the first time based on the fluorinated reverse-phase stationary phase (FC8HL). Superior selectivity between alkaloids and non-alkaloids was achieved in a non-aqueous system, and a simple solvent system containing low-

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A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions

Cited by 48 publications

References 28 publications

LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

A strategy for efficient enrichment of steroidal alkaloids from Fritillaria based on fluorinated reversed‐phase stationary phase

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