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.

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.

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 Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4121
Author(s):  
Md. Josim Uddin ◽  
Daniela Russo ◽  
Md. Anwarul Haque ◽  
Serhat Sezai Çiçek ◽  
Frank D. Sönnichsen ◽  
...  
Keyword(s):  
Significant Activity ◽  
In Vitro Test ◽  
Reference Standard ◽  
Potent Effect ◽  
Spectrometric Data ◽  
Glucosidase Inhibitors ◽  
Vitro Test ◽  
Inhibitory Activities ◽  
Carbohydrate Digestion

In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C13-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6′-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC50 3.4 ± 0.2 μM) compared to the reference standard acarbose (IC50 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 μM, compared to acarbose (IC50 665 ± 42 μM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC50 of 94.7 ± 1.3 and 85.3 ± 2.4 μM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC50 > 100 μM).

α-Glucosidase Inhibitory Activity of the Extracts and Major Phytochemical Components of Smilax glabra Roxb

2020 ◽  
Vol 10 (1) ◽  
pp. 26-32
Author(s):  
Phuong T.M. Nguyen ◽  
Quang V. Ngo ◽  
Minh T.H. Nguyen ◽  
Alan T. Maccarone ◽  
Stephen G. Pyne
Keyword(s):  
Inhibitory Activity ◽  
In Vitro Cytotoxicity ◽  
Antidiabetic Activity ◽  
Ca 125 ◽  
Chemical Structures ◽  
Glucosidase Inhibitors ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Phytochemical Components

Background: A therapeutic approach to treat diabetes is to decrease postprandial hyperglycemia. α-Glucosidase inhibitors from plant sources offer an attractive strategy for the control of hyperglycemia. Smilax glabra Roxb is a medicinal plant found in Asia, including Vietnam, which is used in the treatment of chronic diseases. However, the antidiabetic activity and the identification of α-glucosidase inhibitors from this plant have not been intensively investigated. This research was carried out to determine the α-glucosidase inhibitory activity of the extracts and that of the major phytochemical components of Smilax glabra Roxb. This could lead to further studies on the role of these compounds in hyperglycemia control, as well as identify their potential future applications. Methods: Column chromatography combined with crystallization procedures were used to isolate active fractions and two major compounds. The chemical structures of these compounds were determined by analysis of their NMR spectroscopic data, as well as MS data and comparisons made with the literature data. The α-glucosidase inhibitory activity was determined spectrophotometrically using p-nitrophenyl α-D-glucopyranoside as a substrate. The in vitro cytotoxicity of the isolated compounds and fractions was determined using the MTT assay. Results: The two major compounds, astilbin and 5-O-caffeoylshikimic acid together with two very active fractions, F7 and F8, were isolated from the rhizome. The two major compounds had α- glucosidase inhibitory activities with IC50 values of ca. 125 µg/mL and 38 µg/mL, respectively which are about 4 and 13 folds higher activity than the reference compound acarbose (IC50 of ca. 525 µg/mL). Fractions F7 and F8 showed very promising inhibitory activities towards α-glucosidase with IC50 values of 5.5 and 5.8 µg/mL, respectively. Cytotoxicity data on mouse fibroblast NIH3T3 cells indicated that the active compounds and fractions were not toxic at concentrations that are greater than their respective IC50 values. The α-glucosidase inhibitory activity of 5-Ocaffeoylshikimic acid and that of the two active fractions are reported here for the first time. Conclusion: The two major isolated compounds and fractions, F7 and F8, significantly contribute to the α-glucosidase inhibitory activity of S. glabra Roxb extract. Further work is needed to clarify their modes of action and potential application.

scholarly journals In-Vitro α-Glucosidase Inhibitory Activities of Muntingia Calabura Linn.

2019 ◽  
Vol 7 (4.14) ◽  
pp. 183 ◽  
Author(s):  
N I.I. Nor Azman ◽  
N Hashim ◽  
R Ahmad
Keyword(s):  
Type 2 Diabetes ◽  
Diabetes Type 2 ◽  
Postprandial Hyperglycemia ◽  
Glucosidase Inhibitors ◽  
Biological Studies ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Muntingia Calabura

Muntingia calabura Linn. also known locally as “ceri kampung” is a plant of the family Elaeocarpaceae. The plant has been reported to possess several medicinal properties including reducing high blood pressure, lowering cholesterol level and controlling Type 2 diabetes. Type 2 diabetes is usually related to postprandial hyperglycemia, which is related to the rise of blood sugar level after a meal. This condition can be controlled by α-glucosidase inhibitors which inhibit the enzyme from catalyzing the liberation of glucose from carbohydrates in the digestive tract. Despite many biological studies reported for the plant, its antidiabetic potential has not been widely explored. Thus the aim of this study was to find potential α-glucosidase inhibitors from 16 extracts of M. calabura as a therapeutic approach in decreasing postprandial hyperglycemia. The hexane (Hx), ethyl acetate (Ea), 75% ethanol (Et) and aqueous (Aq) extracts of four parts (fruit, leaf, stem and root) of M. calabura (collected from Bangi, Selangor) were screened for their a-glucosidase inhibitory activities at 50.00, 25.00, 12.50, 6.25, 3.13, 1.56 and 0.78 ppm prepared via two-fold serial dilution against the positive control, acarbose. The aqueous leaf (AqL) and root extracts (AqR) exhibited very strong activities with IC50 values of 0.15 and 0.41 µg/ml  while the other extracts showed strong to moderately strong activities with IC50 values ranging from 1.83-11.66  µg/ml against acarbose (4.3 µg/ml). 

Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking

2019 ◽  
Vol 10 (4) ◽  
pp. 1893-1902 ◽  
Author(s):  
Zi-wan Ning ◽  
Li-xiang Zhai ◽  
Tao Huang ◽  
Jiao Peng ◽  
Die Hu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Homology Model ◽  
Tea Leaves ◽  
Cyclocarya Paliurus ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities ◽  
Tof Ms

11 potential α-glucosidase inhibitors in leaves of Cyclocarya paliurus were quickly identified by UF-UPLC-Q/TOF-MS/MS, and their inhibitory activities were verified in vitro and in vivo, as well as docked with homology model.

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.

Structure - Function Analysis of Peptide Analogs of SQSPA with Respect to α-glucosidase and α-amylase Inhibition

2019 ◽  
Vol 26 (6) ◽  
pp. 403-413
Author(s):  
Mohammed A. Ibrahim ◽  
June C. Serem ◽  
Megan J. Bester ◽  
Albert W. Neitz ◽  
Anabella R.M. Gaspar
Keyword(s):  
Competitive Inhibition ◽  
Function Analysis ◽  
Competitive Inhibitor ◽  
Amino Acid Residues ◽  
Inhibitory Peptide ◽  
Alanine Scanning ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities ◽  
Vitro Analysis

Background: Peptide-based therapeutics offer a unique avenue for the development of novel agents for the treatment of diabetes mellitus including α-glucosidase inhibitors. The peptide, SQSPA, was reported to possess to α -glucosidase inhibitory activity in addition to resistance to Gastrointestinal Tract (GIT) digestion. Methods: In this study, the in silico and in vitro structure-activity analyses of the peptide was conducted using alanine scanning to identify key amino acid residues. Results: The alanine scanning led to four analogs viz; AQSPA, SASPA, SQAPA and SQSAA which were GIT stable. Initially, the peptides were subjected to molecular docking on human α- glucosidase and α -amylase where the binding affinities to the enzymes were in the order; AQSPA>SASPA>SQSPA>SQAPA> SQSAA and AQSPA>SQSAA>SASPA>SQSPA> SQAPA, respectively. Hydrogen bond were important for the binding of all peptides but SASPA and AQSPA had the highest hydrogen bonds interactions with the α-glucosidase and α-amylase, respectively. In vitro analysis revealed that the α -glucosidase and α-amylase inhibitory activities of the peptides were in the order AQSPA>SQSPA>SQAPA>SASPA>SQSAA and AQSPA>SASPA> SQAPA>SQSPA>SQSAA, respectively. Using inhibition kinetics, SQSPA was a mixed inhibitor of α-glucosidase while AQSPA, SQAPA and SQSAA showed non-competitive inhibition. For α- amylase inhibition, SQSPA was a non-competitive inhibitor while AQSPA and SQSAA were mixed inhibitors; SASPA and SQAPA showed uncompetitive inhibition. Conclusion: The results indicated that P4 and Q2 are important requirements for the α-glucosidase and α-amylase inhibitory activities of the parent peptide, SQSPA. Furthermore, alanine scanning has led to the design of a novel α-glucosidase inhibitory peptide, AQSPA, with increased activities.

Study on the interaction of 1,5-diaryl pyrrole derivatives with α-glucosidase; synthesis, molecular docking, and kinetic study

2019 ◽  
Vol 15 ◽  
Author(s):  
Tadesse Bekele Tafesse ◽  
Ebrahim Saeedian Moghadam ◽  
Mohammed Hussen Bule ◽  
Mohammad Ali Faramarzi ◽  
Mohammad Abdollahi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kinetic Studies ◽  
Postprandial Hyperglycemia ◽  
Binding Energies ◽  
Potential Candidate ◽  
Pyrrole Derivatives ◽  
Standard Drug ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

Background: The delaying of absorption of glucose is one of the principal therapeutic approaches of type 2 diabetes. α-glucosidase inhibitors compete with the α-glucosidase enzyme activity, which helps to reduce the conversion of carbohydrates into glucose and thereby control the postprandial hyperglycemia incidence. Objective: The aim of this study was to synthesize a series of novel 1,5-diphenyl pyrrole derivatives and evaluate their in vitro α-glucosidase inhibitory activities. Methods: Compounds were synthesized through a multistep reaction and were evaluated for α-glucosidase inhibitory activities. Molecular docking and kinetic studies were carried out to predict the mode of binding and mechanism of inhibition for the most active compounds, 5g and 5b, against α-glucosidase. Results: Synthesized compounds showed good in vitro α-glucosidase inhibitory activity with IC50 values in the range of (117.5 ± 3.8 to 426.0 ± 10.2 µM) as compared to acarbose, the standard drug, (750 ± 8.7 µM). Compound 5g (117.5 ± 3.8 µM) ascertained as the most potent inhibitor of α-glucosidase in a competitive mode. The binding energies of compounds 5g and 5b (119.0 ± 7.5 µM), as observed from the best docking conformations, indicates that they have a lower free binding energy (-3.26 kcal/mol and -3.0 kcal/mol, respectively) than acarbose (2.47 kcal/mol). Conclusion: The results of our study reveal that the synthesized compounds are a potential candidate for α-glucosidase inhibitors for the management of postprandial hyperglycemia for further investigation.

Synthesis and Biological Activity of Novel Deoxynojirimycin Derivatives as Potent α-Glucosidase Inhibitors

2013 ◽  
Vol 68 (4) ◽  
pp. 383-390 ◽  
Keyword(s):  
Biological Activity ◽  
Kinetic Parameters ◽  
Competitive Inhibitor ◽  
Skeletal Structures ◽  
Glucosidase Inhibitors ◽  
Ic50 Value ◽  
Inhibitory Activities ◽  
Derivatives Of

Thirteen 1-deoxynojirimycin (DNJ) derivatives of five different skeletal structures were designed and synthesized. The newly synthesized compounds were evaluated using an in vitro a- glucosidase assay, and kinetic parameters (Ki, IC50) were measured. Some DNJ derivatives showed weak a-glucosidase inhibitory activities, and the compounds 1-(3-benzyloxy-2-hydroxypropyl)- 2-hydroxymethyl-piperidine-3,4,5-triol (2a) and 1-{3-[1-(4-fluorophenyl)-1H-[1,2,3]triazol-4-ylmethoxy]- 2-hydroxypropyl}-2-hydroxymethyl-piperidine-3,4,5-triol (13d) showed activities comparable to that of DNJ. While 2a was found to be a reversible, non-competitive inhibitor of a-glucosidase with a Ki value of 1.56X10-4 M and an IC50 value of 3.07X10x4 M, 13d was a reversible, competitive inhibitor of a-glucosidase with a Ki value of 2.08X10-4 M and an IC50 value of 3.31X10-4 M.

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