Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies

Barakat, Assem; Islam, Mohammad Shahidul; Al‐Majid, Abdullah Mohammed; Ghabbour, Hazem A.; Yousuf, Sammer; Ashraf, Muhammad Waqar; Shaikh, Nimra Naveed; Choudhary, M. Iqbal; Khalil, Ruqaiya; Ul-Haq, Zaheer

doi:10.1016/j.bioorg.2016.07.009

Cited by 45 publications

(22 citation statements)

References 32 publications

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“…The inhibition of this compound may be due to pyrimidin and pyran rings. [12][13][14][15][16][17][18][19] Our results agree with Najafian 11) he reported that curcumin inhibited α-amylase with an half maximal inhibitory concentration IC 50 value 51.32 µM. Curcumin at different concentrations, i.e., 10, 50, 100 µg showed dose dependent effect where as the standard indomethacin at 50 and 100 µg exhibited much higher activity.…”

Section: α-Amylase Inhibitory Activity By Curcumin Derivativessupporting

confidence: 86%

“…10) Since curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) could be viewed as a flavonoid of polyphenolic compounds, in this investigation we researched the inhibitory effect of curcumin on α-amylase and the effect of curcumin orally on blood glucose levels in streptozotocin (STZ) induced diabetic and normal rats. 11) Pyrimidines exhibit a wide broad as biologically active agents they showed antioxidant, 12) antifungal, 13) antibacterial, 14) antihypertensive, 15) antitumor, 16) activity. Also pyranone which is six membered oxygenated unsaturated ester heterocyclic compounds that shares chemical and physical properties reminiscent of alkene and aromatic compounds showed a wide range of biological activity as antileukemic, 17) antitumor, 18) anti-fungal 19) inhibiting, human immunodeficiency virus (HIV) protease 20) qualities also it was found that In the last several decades, cyclohexenone derivatives have received considerable attention due to their wide range of applications.…”

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confidence: 99%

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Conversion of Curcumin into Heterocyclic Compounds as Potent Anti-diabetic and Anti-histamine Agents

Nabil

El-Rahman

Al-Jameel

et al. 2018

Biological & Pharmaceutical Bulletin

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Potential biologically active derivatives of the curcumin were prepared by the cyclocondensation reaction cyclohexanone 2, imino pyrimidine 3, pyrmidinones 4, thiopyrimidine 6 and pyranone 5, 7 when treated with acetylacetone, guanidine, ureaethylcyanoacetate, thiourea and ethylacetoacetate, respectively. The structures of compounds (2-7) were elucidated by means of microanalysis as well as spectral measurements such as IR, H-NMR, MS. The anti-diabetic potential of curcumin derivatives were evaluated by assessing amylase inhibition assay, also inhibition of histamine release activity of curcumin derivatives were assessed by U937 human monocytes. The results for amylase inhibition activity revels that the curcumin inhibits α-amylase in a concentration dependent manner. Compounds 4 and 5 exhibited significant inhibitory activity against amylase enzyme and was comparable with that of acrabose. Also, compounds 5, 6 and 7 exhibited significant inhibitory activity against histamine. Our results concluded that curcumin pyrmidinones and pyranone derivatives have highly effects as anti-diabetic and anti-histamine activities.

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Section: α-Amylase Inhibitory Activity By Curcumin Derivativessupporting

confidence: 86%

mentioning

confidence: 99%

Conversion of Curcumin into Heterocyclic Compounds as Potent Anti-diabetic and Anti-histamine Agents

Nabil

El-Rahman

Al-Jameel

et al. 2018

Biological & Pharmaceutical Bulletin

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“…α‐Glucosidase, a critical enzyme for the digestion of carbohydrates, catalyzes the cleavage of absorbable monosaccharides, beginning from disaccharides and oligosaccharides . The functions of α‐glucosidase for mammals contain intestinal digestion of dietary carbohydrates, glycogen degradation, and glycoprotein folding and maturation . Besides, the inhibition of α‐glucosidases and related enzymes has a major role in the treatment of diabetes, human immunodeficiency virus (HIV/AIDS), cancer, and other degenerative diseases .…”

Section: Introductionmentioning

confidence: 99%

A new dinuclear copper (II) complex of 2,5–Furandicarboxyclic acid with 4(5)‐Methylimidazole as a high potential α‐glucosidase inhibitor: Synthesis, Crystal structure, Cytotoxicity study, and TD/DFT calculations

Avcı

Altürk

Sönmez

et al. 2019

Applied Organom Chemis

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A new dinuclear copper (II) complex of 2,5–furandicarboxyclic acid with 4(5)‐methylimidazole, [Cu (FDCA)((4(5)MeI)2]2·2H2O, was synthesized, and its structure characterized by XRD, FT–IR and UV–Vis spectroscopic techniques. The α‐glucosidase inhibition and cytotoxicity study of the synthesized Cu (II) complex were determined by IC50 values. The optimized geometry and vibrational harmonic frequencies for the Cu (II) complex were obtained by using Density Functional Theory (DFT) of HSEh1PBE/6–311++G(d,p)/LanL2DZ level. TD‐DFT/HSEh1PBE/6–311++G(d,p)/LanL2DZ level with CPCM model was applied to examine the electronic spectral properties and major contributions were determined via Swizard program. To investigate linear and nonlinear optical behavior of the synthesized Cu (II) complex, the α, Δα and χ(1)/β, γ and χ(3) parameters called linear/nonlinear optical parameters in gas phase and ethanol solvent were computed at the same level and basis set. Furthermore, molecular electrostatic potential (MEP) surface was determined by using the same level. The docking study of the Cu (II) complex to the binding site of the target protein (the template structure S. cerevisiae isomaltase) is fulfilled. Natural bond orbital (NBO) analysis was used to investigate the hyperconjugative interactions, inter‐ and intra‐molecular bonding and to determine coordination around Cu (II) ion. Finally, present work is the first remarkable scientific report of mixed‐ligand (H2FDCA and 4(5)MeI) Cu (II) complex as novel drug candidate for DM II. It is also determined that microscopic third−NLO parameters for the Cu (II) complex is remarkable.

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“…Carboxylate carbonyl oxygen interacted similarly with Arg600 whereas position-3 NH interacted with catalytic residues Glu451 and Tyr508. However, pyrimidinetriones (barbituric acid) [236,237], exhibited inferior potencies compared to standard D-SAL (IC 50 ¼ 45.75 mM), despite their similar binding interactions as compound 159 with active site residues and non-cytotoxicity to 3T3 cells. In a predating study, the structural homolog of pyrimidinone, quinazolinone [238], exhibited a unique trend in inhibitory potency against E.Coli bGLU with significant tolerance for lipophilic alkoxy groups, although poor activity with methyl substituent persisted.…”

Section: Pyridinone Pyrimidinones and Quinazolinonementioning

confidence: 99%

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

Awolade

Cele

Kerru

et al. 2020

European Journal of Medicinal Chemistry

107

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BiomarkerEnzyme inhibition Molecular target Structure activity relationship a b s t r a c tThe emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, b-glucuronidase (bGLU) e a lysosomal acid hydrolase responsible for the catalytic deconjugation of b-D-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of bGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of bGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved bGLU inhibitory potency and the development of new therapeutic agents in consequential.

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Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies

Cited by 45 publications

References 32 publications

Conversion of Curcumin into Heterocyclic Compounds as Potent Anti-diabetic and Anti-histamine Agents

Conversion of Curcumin into Heterocyclic Compounds as Potent Anti-diabetic and Anti-histamine Agents

A new dinuclear copper (II) complex of 2,5–Furandicarboxyclic acid with 4(5)‐Methylimidazole as a high potential α‐glucosidase inhibitor: Synthesis, Crystal structure, Cytotoxicity study, and TD/DFT calculations

Therapeutic significance of β-glucuronidase activity and its inhibitors: A review

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