New Biscoumarin Derivatives as Potent α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, Kinetic Analysis, and Docking Study

Mohammadi‐Khanaposhtani, Maryam; Yahyavi, Hoda; Barzegari, Ebrahim; Imanparast, Somaye; Heravi, Majid Μ.; Faramarzi, Mohammad Ali; Foroumadi, Alireza; Adibi, Hos­sein; Larijani, Bagher; Mahdavi, Mohammad

doi:10.1080/10406638.2018.1509359

Cited by 33 publications

(27 citation statements)

References 22 publications

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“…The Autodock Tools (version 1.5.6) was applied to docking study and as described in our previous works, a modeled α‐glucosidase was used as target enzyme [18] . In the previous works has been mentioned our positive control, acarbose, established hydrogen bonds with the active site residues Asn241, Thr301, Glu304, Thr307, Ser308, Pro309, Arg312, and Gln322 and a hydrophobic interaction with His279 [18] …”

Section: Resultsmentioning

confidence: 99%

Synthesis, α‐glucosidase Inhibition, in silico Pharmacokinetic, and Docking Studies Of Thieno[2,3‐b]Quinoline‐Acetamide Derivatives as New Anti‐Diabetic Agents

Mohammadi‐Khanaposhtani

Noori

Valizadeh

et al. 2022

ChemistrySelect

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In this work, novel anti‐α‐glucosidase agents, thieno[2,3‐b]quinoline‐acetamide derivatives 5 a–m have been designed and synthesized. These compounds were evaluated in vitro against yeast α‐glucosidase. Most of the title new compounds exhibited a significant α‐glucosidase inhibitory activity in comparison to positive control, acarbose. In this regards, the most potent compound amongst the tested compounds, compound 5 k, with IC50=48.66±0.02 μM was 15.6‐fold more potent than acarbose. Compound 5 k was a competitive inhibitor into α‐glucosidase and interacted with important residues of the active site of this enzyme. Three most potent compounds among the newly synthesized compounds 5 j–k and 5 m were evaluated in silico in term of the oral druglikeness and pharmacokinetic properties. The obtained results predicted that these compounds had satisfactory oral druglikeness and pharmacokinetic properties.

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Section: Resultsmentioning

confidence: 99%

Synthesis, α‐glucosidase Inhibition, in silico Pharmacokinetic, and Docking Studies Of Thieno[2,3‐b]Quinoline‐Acetamide Derivatives as New Anti‐Diabetic Agents

Mohammadi‐Khanaposhtani

Noori

Valizadeh

et al. 2022

ChemistrySelect

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“…All experiments were performed at least three times. Dock Tools (version 1.5.6) to study ligand-enzyme interactions 21,80 . Briefly, crystal structures of isomaltase from Saccharomyces cerevisiae (PDB code 3A4A), with 72% identical and shares 85% similarity with the Saccharomyces cerevisiae α-glucosidase, was designated for building modeled α-glucosidase.…”

Section: Chemistrymentioning

confidence: 99%

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Peytam

Adib

Shourgeshty

et al. 2020

Sci Rep

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In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC 50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC 50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. Recently, the world health organization (WHO) has identified the diabetes mellitus (DM) as a critical health challenge in the 21st century. The prevalence of diabetes has been increasing at alarming rate over the past three decades. This metabolic disorder, characterized by chronic hyperglycemia, leads to further severe damages like abnormally great thrust, excessive appetite, overweigh, blindness, excessive urination, cardiovascular complications, as well as renal and neurodegenerative diseases 1-6. There are three main diabetes types among which type 2 or non-insulin dependent (T2DM) is the most common one, mainly treated by controlling the digestive enzyme activities such as α-glucosidase 7-9. α-Glucosidase, found in the brush-border surface membrane of intestinal cells, plays catalyzing role in the carbohydrate digestion process by which the postprandial blood glucose levels increases. Preventing the glucose release in the bloodstream, the α-glucosidase inhibitors control T2DM 10. Additionally, this enzyme has a pivotal role in the biosynthesis of glycoprotein, therefore, its inhibitors have possessed anticancer, antitumor, antiviral, and immunoregulatory properties 11-15. Acrabose, miglitol, voglibose, and deoxynojirimycin have clinically been used to restrict the α-glucosidase activity 16. Considering the side effects and absorption problems associated with these drugs, new scaffolds should be synthesized and evaluated by medicinal chemists to extend the library of compounds 17-25. Pyrazoles are common structural motif in numerous drugs 26 and biologically active compounds showing activities such as anti-cancer 27,28 , anti-inflammatory 29 , anti-hypertensive 30 , cannabinoid receptor antagonist 31 , dopaminergic receptor antagonist 32 , and α-glucosidase inhibitors 33. Pyrazoles have been used to synthesize

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“…Biscoumarins have innumerable enzyme inhibitory action like steroid sulfatase inhibitors, urease inhibitors, α-glucosidase inhibitors, α-amylase inhibitors, aromatase inhibitors, c-Met inhibitors and HIV-1 integrase inhibition. In view of that, Khanaposhtani and colleagues [102] have developed library of biscoumarins (Scheme 18) using 4-aminocoumarin and various substituted benzaldehydes and assessed in vitro α-glucosidase inhibitory activity. The compounds 16c and 16k were found to be most potent among them with IC 50 value of 20.0 � 0.7 and 39.8 � 0.9 mM, respectively.…”

Section: Enzyme Inhibitory Actionmentioning

confidence: 99%

An Insight View on Synthetic Protocol, Mechanistic and Biological Aspects of Biscoumarin Derivatives

2019

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Biscoumarin has emerged as one of the most unique and valuable moiety in the field of synthetic as well as in medicinal chemistry. This moiety has been examined for the designing of potent derivatives and hybrids with other moieties and substituents exhibiting a myriad of medicinal properties. These far‐flung characteristics enthralled the researchers to discover various methods for the synthesis of biscoumarin nucleus and its derivatives from 4‐hydroxycoumarin and varieties of aldehydes using different types of catalysts to improve the selectivity, purity and yield of the products. Moreover, liberal scope is available for this structural unit which needs to be explored by chemists for the advancement of new potential drug candidates. This article summarizes the current eco‐benign pathways for the synthetic strategies of biscoumarins under various reaction conditions viz. solid supported catalyst, ionic liquid, nanoparticles, Lewis acid, heteropolyacids, nanocomposites etc.

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New Biscoumarin Derivatives as Potent α-Glucosidase Inhibitors: Synthesis, Biological Evaluation, Kinetic Analysis, and Docking Study

Cited by 33 publications

References 22 publications

Synthesis, α‐glucosidase Inhibition, in silico Pharmacokinetic, and Docking Studies Of Thieno[2,3‐b]Quinoline‐Acetamide Derivatives as New Anti‐Diabetic Agents

Synthesis, α‐glucosidase Inhibition, in silico Pharmacokinetic, and Docking Studies Of Thieno[2,3‐b]Quinoline‐Acetamide Derivatives as New Anti‐Diabetic Agents

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

An Insight View on Synthetic Protocol, Mechanistic and Biological Aspects of Biscoumarin Derivatives

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