Quinazolinone-dihydropyrano[3,2-b]pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic

2021 ◽  
Vol 109 ◽  
pp. 104703
Author(s):  
Maedeh Sherafati ◽  
Roghieh Mirzazadeh ◽  
Ebrahim Barzegari ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Homa Azizian ◽  
...  
Keyword(s):  
Docking Study ◽  
Design Synthesis ◽  
Enzymatic Inhibition ◽  
Glucosidase Inhibitors

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

scholarly journals Design, Synthesis, Molecular Docking, and Kinetic Study of 3-Amino-2,4-Diarylbenzo[4,5]Imidazo[1,2-a]Pyrimidines as Novel, Potent Α-Glucosidase Inhibitor

2021 ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Zahra Emamgholipour ◽  
Maryam Norouzbahari ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kinetic Study ◽  
Docking Study ◽  
Type Ii Diabetes Mellitus ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Drug Candidates ◽  
Glucosidase Inhibitors

Abstract In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a-ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their α-glucosidase inhibitory activities were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which may provide new drug candidates in the treatment of type II diabetes mellitus. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against α-glucosidase (IC50 = 16.4 ± 0.36 μM) which was 45.7 times more potent than acarbose as standard inhibitor (IC50 = 750.0 ± 1.5 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

Design, synthesis and molecular docking study of novel pyrrole-based α-amylase and α-glucosidase inhibitors

2017 ◽  
Vol 26 (10) ◽  
pp. 2675-2691 ◽  
Author(s):  
Nikhil C. Jadhav ◽  
Akshata R. Pahelkar ◽  
Neha V. Desai ◽  
Vikas N. Telvekar
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Glucosidase Inhibitors

Design, synthesis and docking study of novel tetracyclic oxindole derivatives as α-glucosidase inhibitors

2015 ◽  
Vol 25 (7) ◽  
pp. 1471-1475 ◽  
Author(s):  
Kailin Han ◽  
Yashan Li ◽  
Yazhou Zhang ◽  
Yuou Teng ◽  
Ying Ma ◽  
...  
Keyword(s):  
Docking Study ◽  
Design Synthesis ◽  
Glucosidase Inhibitors

Design, synthesis, characterization, enzymatic inhibition evaluations, and docking study of novel quinazolinone derivatives

2021 ◽  
Vol 170 ◽  
pp. 1-12
Author(s):  
Keyvan Pedrood ◽  
Maedeh Sherafati ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Mohammad Sadegh Asgari ◽  
Samanesadat Hosseini ◽  
...  
Keyword(s):  
Docking Study ◽  
Design Synthesis ◽  
Enzymatic Inhibition ◽  
Quinazolinone Derivatives

Design, Synthesis, Antimicrobial Evaluation and Molecular Modeling Study of New 2-mercaptoimidazoles (Series-III)

2019 ◽  
Vol 16 (5) ◽  
pp. 512-521 ◽  
Author(s):  
Nidhi Rani ◽  
Randhir Singh
Keyword(s):  
Sulfonic Acid ◽  
Docking Study ◽  
Molecular Docking Study ◽  
One Pot ◽  
Design Synthesis ◽  
Toluene Sulfonic Acid ◽  
Antimicrobial Evaluation ◽  
Bacteria And Fungi ◽  
High Yields ◽  
Antimicrobial Potency

Background: A series of novel substituted 2-mercaptoimidazoles was synthesised efficiently and in high yields using one-pot synthesis from m-hydroxyacetophenones. Methods: The structures of the newly synthesized compounds were established, their molecular activity was investigated against some bacteria and fungi were further validated using molecular docking study. Results: Reaction of o-hydroxyphenacylbromide (2) with substituted aniline and KSCN, in the presence of catalyst p-toluene sulfonic acid afforded 4(a-r) in good yield. The structure of compounds (4a-r) was confirmed by IR, NMR and MS. Conclusion: The compounds exhibited excellent antimicrobial potency against the tested microorganism.

Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

2020 ◽  
Vol 16 ◽  
Author(s):  
Marjan Mollazadeh ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Yousef Valizadeh ◽  
Afsaneh Zonouzi ◽  
Mohammad Ali Faramarzi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kinetic Study ◽  
Active Site ◽  
Docking Study ◽  
Secondary Amines ◽  
Molecular Docking Study ◽  
Glucosidase Inhibitors ◽  
Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

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