Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines

Iftikhar, Faiza Jan; Yaqoob, Farhana; Tabassum, Nida; Jan, Muhammad; Sadiq, Abdul; Tahir, Saba; Batool, Tahira; Niaz, Basit; Ansari, Farzana Latif; Choudhary, Muhammad Iqbal; Rashid, Umer

doi:10.1016/j.bioorg.2018.05.026

Cited by 55 publications

(27 citation statements)

References 24 publications

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“…For α-glucosidase, docking studies were carried out on homology modelled α-glucosidase reported by our research group 35 . Preparation of ligands, downloaded enzymes, 3D protonation, energy minimization and determination of binding site was carried out by our previously reported methods 35,36 . The view of the docking results and analysis of their surface with graphical representations were done using MOE and discovery studio visualizer 37 .…”

Section: Total Flavonoid Contents (Tfc)mentioning

confidence: 99%

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

Farooq

Mumtaz

Mukhtar

et al. 2020

Sci Rep

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Butea monosperma is one of the extensively used plants in traditional system of medicines for many therapeutic purposes. in this study, the antioxidant activity, α-glucosidase and α-amylase inhibition properties of freeze drying assisted ultrasonicated leaf extracts (hydro-ethanolic) of B. monosperma have been investigated. The findings revealed that 60% ethanolic fraction exhibited high phenolic contents, total flavonoid contents, highest antioxidant activity, and promising α-glucosidase and αamylase inhibitions. the UHpLc-Qtof-MS/MS analysis indicated the presence of notable metabolites of significant medicinal potential including apigenin, apigenin C-hexoside C-pentoside, apigenin Chexoside C-hexoside, apigenin-6,8-di-C-pentoside and genistin etc., in B. monosperma leave extract. Docking studies were carried out to determine the possible role of each phytochemical present in leaf extract. Binding affinity data and interaction pattern of all the possible phytochemicals in leaf extract of B. monosperma revealed that they can inhibit α-amylase and α-glucosidase synergistically to prevent hyperglycemia. Diabetes mellitus [DM] is most rapidly growing metabolic disorder in the world. It is primarily characterized by hyperglycemia which is associated with disturbed metabolism of carbohydrates, proteins and fats. Such metabolic dysfunctions at physiological level are known to cause detrimental health disorders which lead towards sickness and eventually death 1. According to WHO (World Health Organization), it is estimated that this chronic disease has affected nearly 150 million people throughout the world. This number will increase to three hundred million people or more up to 2025 2. The DM type II (DMT-II) is the most abundant form of diabetes and generally involves the phenomenon of insulin insensitivity or low insulin production. The main reasons behind the spread of this global health problem are mainly modern life style, obesity and consumption of high caloric diet. The growing rate of DM in Asian and African countries is two to three times more than the present rate in other countries 3. The role of reactive oxygen species (ROS) is very crucial in DMT-II pathogenesis. The ROS are produced because of electron transfer to oxygen from mitochondrial metabolic activity. The ROS are captured by antioxidants to maintain the redox homeostasis. However, over production or long-time exposure to ROS may create imbalance which further leads to state of oxidative stress. The oxidative stress exerts harmful impacts on bio-molecules to create metabolic dysfunction. The ROS under umbrella of oxidative stress disturbs the structure based activity of antioxidant enzymes to reduce the antioxidant potential of body 4. The ROS are also involved in impaired insulin secretion from pancreas probably due to dysfunction in β-cells 5. The elevated blood glucose level alters the normal functions of proteins through the process of glycation. The role of glycated end products is obvious in health deterioration and their long term existence...

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Section: Total Flavonoid Contents (Tfc)mentioning

confidence: 99%

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

Farooq

Mumtaz

Mukhtar

et al. 2020

Sci Rep

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“…Moreover, in vivo studies on antiangiogenic activity were carried out. This compound proved to be a strong angiogenesis inhibitor [58].…”

Section: Anti-proliferative Effects Of 134-oxadiazole Derivativesmentioning

confidence: 99%

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

2018

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Compounds containing 1,3,4-oxadiazole ring in their structure are characterised by multidirectional biological activity. Their anti-proliferative effects associated with various mechanisms, such as inhibition of growth factors, enzymes, kinases and others, deserve attention. The activity of these compounds was tested on cell lines of various cancers. In most publications, the most active derivatives of 1,3,4-oxadiazole exceeded the effect of reference drugs, so they may become the main new anti-cancer drugs in the future.

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“…This is also obvious from previous reported studies that asymmetric nitrogenous molecules are important building blocks of medicinal importance and may possesses diverse pharmacological potential. [37][38][39][40] Based on the importance of succinimide scaffold and the dire need of the novel drugs, the current study has been designed in an attempt to synthesize potential derivatives of succinimide and to evaluate them for various biological activities including the anti-Alzheimer's and anti-diabetic using in-vitro and in-silico simulation approaches. , and α-glucosidase from Saccharomyces cerevisiae (CAT No.…”

Section: Introductionmentioning

confidence: 99%

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

Ahmad

Ullah

Sadiq

et al. 2020

DDDT

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Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC 50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC 50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC 50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC 50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H 2 O 2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

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Design, synthesis, in-vitro thymidine phosphorylase inhibition, in-vivo antiangiogenic and in-silico studies of C-6 substituted dihydropyrimidines

Cited by 55 publications

References 24 publications

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

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