A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Patel, Krutika; Gadewar, Manoj; Tripathi, Rohit; Prasad, SK; Patel, Dinesh Kumar

doi:10.1016/s2221-1691(12)60116-6

Cited by 214 publications

(131 citation statements)

References 46 publications

(59 reference statements)

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“…The plant extracts containing 59 were traditionally used to treat alimentary tract cancer and malaria in Northwest China [133]. These extracts have a broad spectrum of biological activities, including antimicrobial, antifungal, antitumor, antiplasmodial, antioxidant, antimutagenic, antigenotoxic, as well as hallucinogenic properties [130]. Compound 59 also inhibits topoisomerase I, cyclin-dependent kinases, monoamine oxidase A, and intercalates into DNA [134].…”

Section: Harmine and Derivativesmentioning

confidence: 99%

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Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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Section: Harmine and Derivativesmentioning

confidence: 99%

“…Harmine (59) is a β-carboline alkaloid found in plants, mammalians, insects, and marine organisms [130], e.g., the marine brown alga Melanothamnus afaqhusainii [131,132]. The plant extracts containing 59 were traditionally used to treat alimentary tract cancer and malaria in Northwest China [133].…”

Section: Harmine and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…1 Studies demonstrate that these alkaloids have several pharmacological actions, among them, anticonvulsant, anti-viral, antitumor, anti-proliferative and anti-microbial activity. [1][2][3][4][5] Moreover, β-carbolines act as deoxyribonucleic acid (DNA) intercalating agents and are able to inhibit the topoisomerases I and II enzymes, [6][7][8] which are responsible for regulating processes such as transcription, replication and DNA recombination. 9,10 Due to different activities demonstrated by this class of compounds, we have synthesized and evaluated the biological activities of several derivatives with different substituents at positions 1 and 3 of the β-carboline nucleus.…”

Section: Introductionmentioning

confidence: 99%

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Silva

Savariz

Silva-Júnior

et al. 2016

Journal of the Brazilian Chemical Society

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Quantitative interaction of twelve β-carboline derivatives with calf thymus deoxyribonucleic acid (ctDNA) using spectroscopic techniques was evaluated. The values of the binding constants (K b ) obtained for the complexes formed with the ctDNA ranged from 3.30 × 10 2 to 1.82 × 10 6 mol L −1 , being the β-carbolines with the N,N-dimethylaminophenyl group at position 1 the ones which presented the highest K b values. The binding mode between the β-carbolines evaluated and ctDNA was proposed from the KI assay, competition with ethidium bromide, and DNA thermal denaturation profile (T m ), where it was possible to infer that the evaluated alkaloids interact with ctDNA preferably via intercalation. Additionally, the correlation of K b values obtained with the IC 50 of seven human cancer cell lines was carried out. From this study, it was possible to observe a linear relation among most of the evaluated derivatives, obtaining r 2 values from 0.5360 to 0.9600. In addition, in silico molecular docking was performed to corroborate the experimental results.

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“…[6][7][8] The harmala alkaloid, harmine, is a β-carboline alkaloid that was originally isolated from seeds of Peganum harmala and Banisteropsis caapi, both of which have traditionally been used in ritual and medicinal preparations of the Middle East, Central Asia and South America. 9) Harmine is also found in common plant-derived foods and animal tissues, 10) and it has antiplasmodial, antioxidative, antimutagenic and antigenotoxic activities, as well as antidepressant properties. [11][12][13] Several psychiatric conditions, including depression, are closely associated with the circadian clock.…”

mentioning

confidence: 99%

Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

Kondoh

Yamamoto

Tomita

et al. 2014

Biological & Pharmaceutical Bulletin

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The circadian clock is a cell-autonomous endogenous system that generates circadian rhythms in the behavior and physiology of most organisms. We previously reported that the harmala alkaloid, harmine, lengthens the circadian period of Bmal1 transcription in NIH 3T3 fibroblasts. Clock protein dynamics were examined using real-time reporter assays of PER2::LUC to determine the effects of harmine on the central Key words carboline alkaloid; circadian clock; PER2::LUC protein; real-time reporter assay; suprachiasmatic nucleus The circadian clock is an endogenous cell-autonomous system that generates circadian rhythms in the behavior and physiology of most organisms. The master clock in mammals is located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, 1,2) which controls most aspects of physiology such as sleep-wake cycles, body temperature, hormone secretion, blood pressure and metabolism.3,4) The circadian clock mechanism consists of a network of autoregulatory transcription-based feedback loops that drive the rhythmic expression of clock genes such as Per1, Per2 and Bmal1, 5) and these cell-autonomous and self-sustained oscillators are found not only in the SCN but also in peripheral tissues as well as dissociated cells. Acute induction of the mRNA expression of clock genes plays a critical role in phase shifting the circadian clock both in cells cultured in vitro and in vivo. In addition to transcriptional feedback regulations, some essential roles of post-translational modifications such as phosphorylation and ubiquitination have been reported. [6][7][8] The harmala alkaloid, harmine, is a β-carboline alkaloid that was originally isolated from seeds of Peganum harmala and Banisteropsis caapi, both of which have traditionally been used in ritual and medicinal preparations of the Middle East, Central Asia and South America. 9) Harmine is also found in common plant-derived foods and animal tissues, 10) and it has antiplasmodial, antioxidative, antimutagenic and antigenotoxic activities, as well as antidepressant properties.11-13) Several psychiatric conditions, including depression, are closely associated with the circadian clock.14) Although we previously reported that harmine dose-dependently lengthens the circadian period of Bmal1 expression in NIH 3T3 cells, 15) the effects of harmine on the master clock in the SCN remain unknown. We therefore evaluated clock protein dynamics in neuronal cells and in SCN slices by monitoring PER2::LUC bioluminescence in real-time to determine the effects of harmine on the master clock in the SCN.

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A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

Cited by 214 publications

References 46 publications

Marine Natural Products as Models to Circumvent Multidrug Resistance

Marine Natural Products as Models to Circumvent Multidrug Resistance

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

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