Barbiturate derivatives for managing multifaceted oncogenic pathways: A mini review

Prasher, Parteek; Sharma, Mousmee; Singh, Samarth Pratap; Rawat, Devendra

doi:10.1002/ddr.21761

Cited by 5 publications

(2 citation statements)

References 59 publications

(69 reference statements)

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“…Although there is no direct relationship between the use of XO inhibitors and a good prognosis in cancer treatment, the expression and activity of this enzyme have been negatively associated with a high degree of malignancy and a worse prognosis in some types of cancer, namely of the breast and gastrointestinal tract, in recent years [28,29]. Considering the low cytotoxicity on NHDF cells observed for bis-thiobarbiturate 11, the interest of barbiturate and thiobarbiturate derivatives as anticancer agents [11,13] and the recent work on XO inhibitors with anticancer activity [30], we decided to evaluate the cytotoxicity on NHDF as well as the antiproliferative effects on colorectal adenocarcinoma Caco-2 and breast cancer MCF-7 cell lines for all bis-thiobarbiturates under study. To get a strengthened term of comparison, the anticancer drug 5-FU was used as a positive control.…”

Section: Resultsmentioning

confidence: 99%

“…Firstly synthesized by Adolph von Baeyer in 1864, barbituric acid was the key molecule for developing new derivatives with central nervous system (CNS) depressing activity in the twentieth century [10]. Initially used as anticonvulsant, anxiolytic, sedative-hypnotic and anesthetics [10], barbituric and thiobarbituric acid derivatives have recently been associated with several potential industrial and pharmaceutical/biological applications [10,11] namely as antifungal [12], antibacterial [13][14][15], anticancer [11,13,16,17], antiviral [18], as well as urease [19], XO [13], and helicase inhibitors [20]. Additionally, it has been established that this pyrimidine class of compounds undergoes Knoevenagel condensations with aldehydes to give 5-ylidene derivatives [13,21].…”

Section: Introductionmentioning

confidence: 99%

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Bis-thiobarbiturates as Promising Xanthine Oxidase Inhibitors: Synthesis and Biological Evaluation

et al. 2021

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Xanthine oxidase (XO) is the enzyme responsible for the conversion of endogenous purines into uric acid. Therefore, this enzyme has been associated with pathological conditions caused by hyperuricemia, such as the disease commonly known as gout. Barbiturates and their congeners thiobarbiturates represent a class of heterocyclic drugs capable of influencing neurotransmission. However, in recent years a very large group of potential pharmaceutical and medicinal applications have been related to their structure. This great diversity of biological activities is directly linked to the enormous opportunities found for chemical change off the back of these findings. With this in mind, sixteen bis-thiobarbiturates were synthesized in moderate to excellent reactional yields, and their antioxidant, anti-proliferative, and XO inhibitory activity were evaluated. In general, all bis-thiobarbiturates present a good antioxidant performance and an excellent ability to inhibit XO at a concentration of 30 µM, eight of them are superior to those observed with the reference drug allopurinol (Allo), nevertheless they were not as effective as febuxostat. The most powerful bis-thiobarbiturate within this set showed in vitro IC50 of 1.79 μM, which was about ten-fold better than Allo inhibition, together with suitable low cytotoxicity. In silico molecular properties such as drug-likeness, pharmacokinetics, and toxicity of this promising barbiturate were also analyzed and herein discussed.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bis-thiobarbiturates as Promising Xanthine Oxidase Inhibitors: Synthesis and Biological Evaluation

et al. 2021

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Medicinal chemistry of anthranilic acid derivatives: A mini review

Prasher

Sharma

2021

Drug Development Research

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Anthranilic acid and its analogues present a privileged profile as pharmacophores for the rational development of pharmaceuticals deliberated for managing the pathophysiology and pathogenesis of various diseases. The substitution on anthranilic acid scaffold provides large compound libraries, which enable a comprehensive assessment of the structure activity relationship (SAR) analysis for the identification of hits and leads in a typical drug development paradigm. Besides, their widespread applications as anti‐inflammatory fenamates, the amide and anilide derivatives of anthranilic acid analogues play a central role in the management of several metabolic disorders. In addition, these derivatives of anthranilic acid exhibit interesting antimicrobial, antiviral and insecticidal properties, whereas the derivatives based on anthranilic diamide scaffold present applications as P‐glycoprotein inhibitors for managing the drug resistance in cancer cells. In addition, the anthranilic acid derivatives serve as the inducers of apoptosis, inhibitors of hedgehog signaling pathway, inhibitors of mitogen activated protein kinase pathway, and the inhibitors of aldo‐keto reductase enzymes. The antiviral derivatives of anthranilic acid focus on the inhibition of hepatitis C virus NS5B polymerase to manifest considerable antiviral properties. The anthranilic acid derivatives reportedly present neuroprotective applications by downregulating the key pathways responsible for the manifestation of neuropathological features and neurodegeneration. Nevertheless, the transition metal complexes of anthranilic acid derivatives offer therapeutic applications in diabetes mellitus, and obesity by regulating the activity of α‐glucosidase. The present review demonstrates a critical analysis of the therapeutic profile of the key derivatives of anthranilic acid and its analogues for the rational development of pharmaceuticals and therapeutic molecules.

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Enamino Barbiturates as Antiproliferative and Antimicrobial Agents: Studies on Synthesis, Biological Activities, and Molecular Modeling

Shtaiwi,

Abu Sarhan,

Aljaar

et al. 2024

ChemistrySelect

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In the present study, the aimed enamines 3 a–j were synthesized with yield ranging between 65 and 81 % by the reaction of 5‐((dimethylamino)methylene)‐1,3‐dimethylpyrimidine‐2,4,6(1H,3H,5H) ‐trione (2) with different amines at room temperature (25 °C). The structures of all synthesized compounds were characterized using different spectroscopic techniques. Molecular docking studies of the new compounds 3 a–j were carried out with human estrogen receptor (hER) enzyme to evaluate their activities as an effective drug molecules. It was investigated that the compounds 3 b, 3 e, 3 f and 3 j revealed the best binding affinities. All new compounds were evaluated towards antifungal activities, which conceded that the compound 3 e displayed a remarkable antifungal activity compared to the Fluconazole and Nystatin, and its Minimum Inhibitory Concentration (MIC) found to be 0.011 mM, while for Fluconazole the MIC value exhibited at 0.046 mM. Additionally, the toxicity for the new compounds found to be better than tamoxifen on MCF‐7 cells and among these molecules, the compound 3 e displayed the lowest IC50 value.

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Barbiturate derivatives for managing multifaceted oncogenic pathways: A mini review

Cited by 5 publications

References 59 publications

Bis-thiobarbiturates as Promising Xanthine Oxidase Inhibitors: Synthesis and Biological Evaluation

Bis-thiobarbiturates as Promising Xanthine Oxidase Inhibitors: Synthesis and Biological Evaluation

Medicinal chemistry of anthranilic acid derivatives: A mini review

Enamino Barbiturates as Antiproliferative and Antimicrobial Agents: Studies on Synthesis, Biological Activities, and Molecular Modeling

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