scholarly journals Cinnamoyl Sucrose Esters as Alpha Glucosidase Inhibitors for the Treatment of Diabetes

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 469
Author(s):  
Surabhi Devaraj ◽  
Yew Mun Yip ◽  
Parthasarathi Panda ◽  
Li Lin Ong ◽  
Pooi Wen Kathy Wong ◽  
...  
Keyword(s):  
Side Effects ◽  
Docking Studies ◽  
Inhibition Activity ◽  
Sucrose Esters ◽  
Glucosidase Inhibitors ◽  
Treatment Of Diabetes ◽  
Inhibitory Activities ◽  
Further Development ◽  
High Inhibition

Cinnamoyl sucrose esters (CSEs) were evaluated as AGIs and their enzyme inhibition activity and potency were compared with gold standard acarbose. The inhibition activity of the CSEs against α-glucosidase and α-amylase depended on their structure including the number of the cinnamoyl moieties, their position, and the presence or absence of the acetyl moieties. The inhibitory values of the CSEs 2–9 generally increases in the order of mono-cinnamoyl moieties < di-cinnamoyl ≤ tri-cinnamoyl < tetra-cinnamoyl. This trend was supported from both in vitro and in silico results. Both tetra-cinnamoyl CSEs 5 and 9 showed the highest α-glucosidase inhibitory activities of 77 ± 5%, 74 ± 9%, respectively, against acarbose at 27 ± 4%, and highest α-amylase inhibitory activities of 98 ± 2%, 99 ± 1%, respectively, against acarbose at 93 ± 2%. CSEs 3, 4, 6, 7, 8 showed desired higher inhibition of α-glucosidase than α-amylase suggesting potential for further development as AGIs with reduced side effects. Molecular docking studies on CSEs 5 and 9 attributed the high inhibition of these compounds to multiple π-π interactions and favorable projection of the cinnamoyl moieties (especially O-3 cinnamoyl) in the enzyme pockets. This work proposes CSEs as new AGIs with potentially reduced side effects.

Feruloyl Sucrose Esters: Potent and Selective Inhibitors of α-glucosidase and α-amylase.

2021 ◽  
Vol 28 ◽  
Author(s):  
Surabhi Devaraj ◽  
Yew Mun Yip ◽  
Parthasarathi Panda ◽  
Li Lin Ong ◽  
Pooi Wen Kathy Wong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Blood Glucose ◽  
Side Effects ◽  
Docking Studies ◽  
Sucrose Esters ◽  
Molecular Docking Studies ◽  
Gastrointestinal Side Effects ◽  
Lead Candidate

Introduction: Feruloyl Sucrose Esters (FSEs) are a class of Phenylpropanoid Sucrose Esters (PSEs) widely distributed in plants. They were investigated as potential selective Alpha Glucosidase Inhibitors (AGIs) to eliminate the side effects associated with the current commercial AGIs. The latter effectively lowers blood glucose levels in diabetic patients but causes severe gastrointestinal side effects. Methods: Systematic structure-activity relationship (SAR) studies using in silico, in vitro and in vivo experiments were used to accomplish this aim. FSEs were evaluated for their in vitro inhibition of starch and oligosaccharide digesting enzymes α-glucosidase and α-amylase followed by in silico docking studies to identify the binding modes. A lead candidate, FSE 12 was investigated in an STZ mouse model. Results: All active FSEs showed desired higher % inhibition of α-glucosidase and desired lower inhibition of α-amylase in comparison to AGI gold standard acarbose. This suggests a greater selectivity of the FSEs towards α-glucosidase than α-amylase, which is proposed to eliminate the gastrointestinal side effects. From the in vitro studies, the position and number of the feruloyl substituents on the sucrose core, the aromatic ‘OH’ group, and the diisopropylidene bridges were key determinants of the % inhibition of α-glucosidase and α-amylase. In particular, the diisopropylidene bridges are critical for achieving inhibition selectivity. Molecular docking studies of the FSEs corroborates the in vitro results. The molecular docking studies further reveal that the presence of free aromatic ‘OH’ groups and the substitution at position 3 on the sucrose core are critical for the inhibition of both the enzymes. From the in vitro and molecular docking studies, FSE 12 was selected as a lead candidate for validation in vivo. The oral co-administration of FSE 12 with starch abrogated the increase in post-prandial glucose and significantly reduced blood glucose excursion in STZ-treated mice compared to control (starch only) mice. Conclusion: Our studies reveal the potential of FSEs as selective AGIs for the treatment of diabetes, with a hypothetical reduction of side effects associated with commercial AGIs.

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 Synthesis, in vitro and in silico Studies of Naphthalene Pyrazoline Prop-2-en-1-one Derivatives

2020 ◽  
Vol 32 (8) ◽  
pp. 1849-1856
Author(s):  
B. Prabha ◽  
C. Raja ◽  
S. Nathiya ◽  
M.R. Ezhilarasi
Keyword(s):  
Binding Affinity ◽  
Addition Reaction ◽  
Condensation Reaction ◽  
Docking Studies ◽  
High Drug ◽  
In Silico Studies ◽  
Drug Score ◽  
The Michael Addition ◽  
High Inhibition

The synthesized new naphthalene pyrazoline prop-2-en-1-one derivatives (NDPP 1-8) were obtained by the Michael addition reaction of ethyl propanoate, hydrazine hydrate with NPD as a multicomponent scaffold. (E)-1-(naphthalen-3-yl)-3-phenylprop-2-en-1-one (NPD) was formed from 2-acetyl naphthalene and substituted aldehyde via Claisen-Schmidt condensation reaction. The NDPP skeleton structures were confirmed by infrared, 1H & 13C NMR spectral data and elemental analysis. The structure of NDPP compounds was subjected to molecular docking and ADME studies. The result of ADME prediction, compound NDPP 2, which contains electron withdrawing -Cl group has high drug-likeness value 4.21 than the compounds NDPP 4 and 7 which had electron donating CH3 and OCH3 group shows the drug-likeness value 2.62. The NDPP 2 also has high drug score 0.63 than NDPP 4 and NDPP 7 have drug score 0.60 and 0.69, respectively. Docking studies shows that compound NDPP 5 which also contain electron withdrawing NO2 group has good binding affinity value -8.8 Kcal/mol were docked with 1UAG protein. These compounds showed good drug-likeness value 2.25 and drug score 0.65. in vitro Studies have a high inhibition value for the same NO2 substituted derivative. All the compounds have higher binding affinity value than standards binding affinity value.

Concise synthesis of a new triterpenoid saponin from the roots of Gypsophila oldhamiana and its derivatives as α-glucosidase inhibitors

2016 ◽  
Vol 40 (11) ◽  
pp. 9537-9549 ◽  
Author(s):  
Qingchao Liu ◽  
Tiantian Guo ◽  
Fahui Li ◽  
Dong Li
Keyword(s):  
Triterpenoid Saponin ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

The natural triterpenoid saponin 1 and its derivatives 2–3 were synthesized and exhibited potent inhibitory activities against α-glucosidase in vitro.

Synthesis and biological evaluation of oleanolic acid derivative–chalcone conjugates as α-glucosidase inhibitors

RSC Advances ◽  
2014 ◽  
Vol 4 (21) ◽  
pp. 10862-10874 ◽  
Author(s):  
Chu Tang ◽  
Linhui Zhu ◽  
Yu Chen ◽  
Rui Qin ◽  
ZhiNan Mei ◽  
...  
Keyword(s):  
Acid Derivative ◽  
Oleanolic Acid ◽  
Biological Evaluation ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities ◽  
Synthesis And Biological Evaluation ◽  
Oleanolic Acid Derivative

Series of oleanolic acid derivative–chalcone conjugates were designed, synthesized and their α-glucosidase inhibitory activities were investigatedin vitro.

scholarly journals Synthesis, Anti-Inflammatory Activity and Molecular Docking Studies of 1,4,5,6-Tetrahydropyrimidine-2-Carboxamides

2020 ◽  
Vol 27 (3) ◽  
pp. 353-365
Author(s):  
Volodymyr Ya. Horishny ◽  
Pavlo V. Zadorozhnii ◽  
Ivanna V. Horishnia ◽  
Vasyl S. Matiychuk
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Cox Inhibitors ◽  
White Rats ◽  
Urgent Task ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. The widespread use of NSAIDs is associated with a number of serious side effects and complications observed for both selective and non-selective COX inhibitors. Therefore, the search for new COX inhibitors, which along with their effectiveness will have minimal side effects, is a very important and urgent task. Methods: This work studied the synthesis of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides based on the reaction of 2-morpholin-4-yl-N-(het)aryl-2-thioxoacetamides with 1,3-diaminopropane. All obtained compounds were tested for anti-inflammatory activity in vitro and in silico conditions. All synthesized 1,4,5,6-tetrahydropyrimidine-2-carboxamides were tested for influence on the course of the exudative phase of the inflammatory process based on the carrageenan model of paw edema of laboratory nonlinear heterosexual white rats weighing 220-250 g, using Diclofenac as a reference. Optimization of the geometry of the studied structures and molecular docking was carried out using the ArgusLab 4.0.1 software package. Results: The target products were obtained with yields of 71-98% and easily isolated from the reaction mixture. The best anti-inflammatory activity was found in N-(4-chlorophenyl)-1,4,5,6-tetrahydropyrimidine-2-carboxamide and in N-[4-chloro-3-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydropyrimidine-2-carboxamide, suppression of the inflammatory response was 46.7 and 46.4%, respectively. The results of molecular docking with COX-1 and COX-2 enzymes were in good agreement with the experimental data, R2 ˃ 0.92 and R2 ˃ 0.83, respectively. Conclusion: The compounds under study were shown to be promising as potential anti-inflammatory agents.

scholarly journals Investigation of ginger (Zingiber officinale) aqueous extract as an anti-diabetic in vitro

2021 ◽  
Vol 913 (1) ◽  
pp. 012108
Author(s):  
P Pakan ◽  
K Lidia ◽  
M Riwu
Keyword(s):  
Side Effects ◽  
Glucose Uptake ◽  
Aqueous Extract ◽  
Zingiber Officinale ◽  
Control Group ◽  
Plain Water ◽  
Ginger Extract ◽  
Mouse Tissues ◽  
Treatment Of Diabetes

Abstract Diabetes mellitus is a condition of metabolic imbalance, indicated by a high level of blood glucose (hyperglycemia) resulting from a reduction of insulin secretion, action, or both. People with diabetes suffer from a lack or deficiency of insulin or insulin resistance. The metabolic imbalances are often not satisfactorily corrected using conventional medicines and even cause some side effects, which can be detrimental. Research on herbal medicines for the treatment of diabetes is urged by the need to reduce unwanted side effects common with conventional medicines/treatments used in glucose regulation. This study aims to investigate the antidiabetic effect of Ginger (Zingiber officinale) aqueous extract in improving the glucose uptake in mouse tissues in vitro. This study is a true experimental research design with a posttest-only control group design. There were three groups of mice in this study: the control group, which were only given plain water; the second group of mice with 5% aqueous ginger extract and the last group were given 25% aqueous ginger extract. All groups were given treatment for four consecutive weeks, then dissected their cardiac muscle, skeletal muscle, pancreas, and liver tissues to analyze the glucose uptake. The result showed that both the ginger aqueous extract groups were able to increase the glucose uptake of the mice. In conclusion, this research has shown that aqueous ginger extract may have improved the glucose uptake in most tissues of the mice in the groups. Therefore, ginger could have great potential as an alternative way in the treatment of diabetes type 2.

scholarly journals Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4941
Author(s):  
Ivana I. Jevtić ◽  
Thu Hang Lai ◽  
Jelena Z. Penjišević ◽  
Sladjana Dukić-Stefanović ◽  
Deana B. Andrić ◽  
...  
Keyword(s):  
Binding Assay ◽  
Docking Studies ◽  
Emission Tomography ◽  
Binding Affinities ◽  
The Novel ◽  
Competitive Binding Assay ◽  
Mao B ◽  
Positron Emission ◽  
Further Development

Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.

Evaluation of in-vitro antidiabetic activity of leaf juice of Plectranthus amboinicus (lour.)

2020 ◽  
Vol 10 (1) ◽  
pp. 9-17
Author(s):  
Pavan Kumar Kurakula ◽  
Tharun D ◽  
Mahantesh S ◽  
Krishna O ◽  
Sudheer A ◽  
...  
Keyword(s):  
Side Effects ◽  
Enzyme Inhibitors ◽  
Antidiabetic Activity ◽  
Albino Rat ◽  
Glucosidase Inhibitors ◽  
Ic50 Values ◽  
Gastrointestinal Side Effects ◽  
Plectranthus Amboinicus ◽  
Leaf Juice

Diabetes mellitus ‘the disease of modern civilization’ is characterized by chronic hyperglycaemia. The management of elevated post prandial glucose is critical to control the sequale of complications and α-amylase, α-glucosidases are responsible for elevated plasma glucose. Enzyme inhibitors in current clinical practice like acarbose, voglibose etc. are known to cause various gastrointestinal side effects. The present study was aimed to screen for potential α-amylase and α-glucosidase inhibitors from natural sources by in–vitro antidiabetic assays to overcome the side effects and toxicity. Different concentrations of leaf juice of Plectranthus amboinicus Lour. (20, 40, 60, 80 &amp;100 μg/ml) were tested against fungal α-amylase and α-glucosidases isolated from albino rat small intestine and a prominent dose dependent inhibition of the enzymes was observed comparable with the marketed product, Acarbose. The IC50 values of LJPA and acarbose on fungal α-amylase was found to be 83.15 &amp;52.15 μg/ml respectively. The IC50 values of LJPA and acarbose on α-glucosidase was found to be 92.44 &amp;54.84 μg/ml respectively. The protein concentration of leaf juice was found to be 10.6 mg/ml.

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