Inhibition of catechol-O-methyltransferase (COMT) by some plant-derived alkaloids and phenolics

Yalçın, Dilek; Bayraktar, Oğuz

doi:10.1016/j.molcatb.2009.04.014

Cited by 22 publications

(10 citation statements)

References 18 publications

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“…It was shown in another in vitro study that the extract of P. harmala has the ability to inhibit catechol-O-methyltransferase and thereby the methylation of catecholamines with a mixed type mechanism. [ 34 ] All of these effects represent an idea that P. harmala and its derivatives could be used for treatment of mood disorders and are potent alternatives for current anti-depression drugs.…”

Section: Effects On Nervous Systemmentioning

confidence: 99%

Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids

Moloudizargari¹,

Mikaili²,

et al. 2013

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Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue).

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Section: Effects On Nervous Systemmentioning

confidence: 99%

Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids

Moloudizargari¹,

Mikaili²,

et al. 2013

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“…5,7a,12 Our results corroborate with the results of other studies that have also highlighted the inhibitory effects of several commercially available compounds. 11,13 Other studies have revealed that inhibition of methyltransferases has a significant effect on the dengue virus infection. 13,14 In order to validate the differences between eight different concentrations, we employed the ANOVA test.…”

Section: Effect Of Various Compounds On Mtase Activitymentioning

confidence: 99%

“…11,13 Other studies have revealed that inhibition of methyltransferases has a significant effect on the dengue virus infection. 13,14 In order to validate the differences between eight different concentrations, we employed the ANOVA test. Results of ANOVA showed statistically significant differences across eight different concentrations for both Azacitidine and Zebularine ( Figure 2B and 2C).…”

Section: Effect Of Various Compounds On Mtase Activitymentioning

confidence: 99%

“…Other authors such as Yalcin and Bayraktar also reported time-dependent inactivation of methyltransferase as the degree of inhibition increased with time. [11][12][13]15,16 CONCLUSION These outcomes are significant as a beginning stage for further illustration of the specific components of the antiviral movement and to pick up the expected information to additionally grow new, increasingly intense and safe medications to decrease the diseases brought about by this pertinent pathogen. The two compounds were found as the most potent inhibitors among the five different screened compounds.…”

Section: Time-dependent Inhibitionmentioning

confidence: 99%

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Pharmacological Modulation of Flavivirus Methyltransferase Activity of Dengue Virus (DEV)

Alwabli¹,

Alattas²,

Alhebshi³

et al. 2019

IJPER

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Background:The occurrence of dengue fever plagues has expanded significantly in the course of the most recent couple of decades. Be that as it may, no immunization or antiviral treatments are accessible. In this manner, the requirement for protected and successful antiviral medications have turned out to be essential. Aim: Methyltransferases, with their altered enzymatic action, have been found associated with several diseases or infections. It has been observed that the dengue virus infection is correlated with the hyperactivity of methyltransferase. In the current study, we proposed to investigate the inhibitory effects of commercially available compounds on the methyltransferase activity. Materials and Methods: Evaluation of methyltransferase activity of the purified enzyme and their inhibitors was carried out using Methyltransferase Activity Assay Kit (Colorimetric). Results: Among the screened components, we identify two effective compounds that revealed significant effect against flavivirus methyltransferase activity. Further, time-dependent inhibition profiles for both compounds revealed that preincubation of fractions of Azacitidine and Zebularine for different time windows showed time-dependent inactivation of methyltransferase as the degree of inhibition increased with time. Conclusion: We conclude that both Azacitidine and Zebularine may be emerging as possible suitable drugs for the treatment of dengue virus infection. Cite this article: Alwabli AS, Alattas SG, Alhebshi AM, Zabermawi NM, Kaneez F, Azhar EI, Alkenani N, Al-ghmady K, Qadri I. Pharmacological Modulation of Flavivirus Methyltransferase Activity of Dengue Virus (DEV). Indian J of Pharmaceutical Education and Research. 2019;53(3 Suppl 2):s432-s436. PICTORIAL ABSTRACT SUMMARYThis investigation, clearly shows that Azacitidine and Zebularine could be an elective second, possible, of a drug in the treatment of Dengue (DENV) infection.

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“…Several phytochemicals with catecholic structures have been studied for their inhibitory effects on COMT. Flavonols, isoflavones, catechins, alkaloids, and polyphenolic acids have been evaluated as COMT inhibitors and investigated for their implication in chemical-induced genotoxicity or their therapeutic value in treating Parkinson’s disease [ 16 , 17 , 18 , 19 ]. However, effects of phytochemicals belonging to the lignan class on COMT activity have not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

Nordihydroguaiaretic Acid as a Novel Substrate and Inhibitor of Catechol O-Methyltransferase Modulates 4-Hydroxyestradiol-Induced Cyto- and Genotoxicity in MCF-7 Cells

et al. 2021

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Nordihydroguaiaretic acid (NDGA) is a major lignan metabolite found in Larrea spp., which are widely used in South America to treat various diseases. In breast tissue, estradiol is metabolized to the catechol estrogens such as 4-hydroxyestradiol (4-OHE2), which have been proposed to be cancer initiators potentially involved in mammary carcinogenesis. Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens to their less toxic methoxy derivatives, such as 4-O-methylestradiol (4-MeOE2). The present study investigated the novel biological activities of NDGA in relation to COMT and the effects of COMT inhibition by NDGA on 4-OHE2-induced cyto- and genotoxicity in MCF-7 human breast cancer cells. Two methoxylated metabolites of NDGA, 3-O-methylNDGA (3-MNDGA) and 4-O-methyl NDGA (4-MNDGA), were identified in the reaction mixture containing human recombinant COMT, NDGA, and cofactors. Km values for the COMT-catalyzed metabolism of NDGA were 2.6 µM and 2.2 µM for 3-MNDGA and 4-MNDGA, respectively. The COMT-catalyzed methylation of 4-OHE2 was inhibited by NDGA at an IC50 of 22.4 µM in a mixed-type mode of inhibition by double reciprocal plot analysis. Molecular docking studies predicted that NDGA would adopt a stable conformation at the COMT active site, mainly owing to the hydrogen bond network. NDGA is likely both a substrate for and an inhibitor of COMT. Comet and apurinic/apyrimidinic site quantitation assays, cell death, and apoptosis in MCF-7 cells showed that NDGA decreased COMT-mediated formation of 4-MeOE2 and increased 4-OHE2-induced DNA damage and cytotoxicity. Thus, NDGA has the potential to reduce COMT activity in mammary tissues and prevent the inactivation of mutagenic estradiol metabolites, thereby increasing catechol estrogen-induced genotoxicities.

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Inhibition of catechol-O-methyltransferase (COMT) by some plant-derived alkaloids and phenolics

Cited by 22 publications

References 18 publications

Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids

Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids

Pharmacological Modulation of Flavivirus Methyltransferase Activity of Dengue Virus (DEV)

Nordihydroguaiaretic Acid as a Novel Substrate and Inhibitor of Catechol O-Methyltransferase Modulates 4-Hydroxyestradiol-Induced Cyto- and Genotoxicity in MCF-7 Cells

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