Indane-1,3-diones: as potential and selective α-glucosidase inhibitors, their synthesis, in vitro and in silico studies.

2020 ◽  
Vol 16 ◽  
Author(s):  
Asma Mukhtar ◽  
Shazia Shah ◽  
Kanwal ◽  
Shehryar Hameed ◽  
Khalid Mohammed Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Synthetic Molecules ◽  
Ic50 Values

Background: Diabetes mellitus is one the most chronic metabolic disorder. Since past few years our research group had synthesized and evaluated libraries of heterocyclic compounds against α and β-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and βglucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Method: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and β-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against α-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β-glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

scholarly journals MCF-7 Human Breast Adenocarcinoma Anticancer and Antimicrobial, in silico Docking and ADME Prediction Studies of Furan Moiety Containing Substituted 2-Aminopyrimidine Derivatives

2021 ◽  
Vol 33 (7) ◽  
pp. 1504-1512
Author(s):  
Manju Mathew ◽  
Muthuvel Ramanathan Ezhilarasi
Keyword(s):  
In Silico ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Bacterial Strains ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Furan Moiety ◽  
Different Strains

A series of 4(5-(4-chlorophenyl)furan-2-yl)-6-phenylpyrimidin-2-amine derivatives (5a-h) were synthesized from 2-(4-chlorophenyl)-5-styrylfuran (3a-h) with guanidine nitrate in absolute ethanol under conventional method and evaluated for their in vitro anticancer, antimicrobial activities and in silico studies. The chemical structure of the furan moiety containing substituted amino pyrimidine derivatives (5a-h) were elucidated from spectroscopic analysis like infrared, 1H & 13C NMR spectral data and CHN analysis. in silico docking studies were predicted for the synthesized compounds (5a-h) using bacterial protein 1UAG and in silico ADME predictions were also carried for the synthesized compounds (5a-h). The in vitro anticancer study was carried the compound 5b by MMT assay. Compound 5b shows the LC50 value of 120.15 ± 0.003 μg/mL. in vitro Antimicrobial activities were screened for the compounds (5a-h) using different strains. Compound 5h has electron withdrawing group in benzene ring substituted in the para position showed good antimicrobial activity against all the bacterial strains and fungal strains. in silico studies, compound 5h shows excellent docking score (-9.7 kcal/mol) compared with ciprofloxacin (-7.8 kcal/mol).

The inhibitory Effects of Some Artificial Food Colorings on α-amylase and α-glucosidase: In Vitro and In Silico Studies

2021 ◽  
Vol 17 ◽  
Author(s):  
Reguia Mahfoudi ◽  
Amar Djeridane ◽  
Djilali Tahri ◽  
Mohamed Yousfi
Keyword(s):  
In Silico ◽  
Hydrophobic Interactions ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Qsar Study ◽  
Molegro Virtual Docker ◽  
Artificial Food ◽  
In Silico Studies ◽  
Ic50 Values

Background: Inhibition of α-amylase and α-glucosidase is considered as an important therapeutic target to manage type 2 diabetes mellitus (T2DM), reducing postprandial hyperglycemia (PPHG). Objective: The present work explored the antidiabetic activities of five artificial food colorings by α-amylase and α-glucosidase enzyme inhibition in vitro and in Silico. Methods: In this study, inhibition of α-amylase and α-glucosidase were evaluated. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (food colorings) was followed by QSAR and molecular docking studies. Results: The in vitro results obtained show that the blue patent (SIN131) exhibited more potent inhibition with IC50 values of 0.03± 0.01 mM and 0.014±0.001 mM against α-amylase and α-glucosidase inhibition respectively compared to acarbose. The QSAR study found a strong correlation between IC50 values with four molecular descriptors. This linear regression confirms that a strong polarity (Apol) and a low hydrophobia (ALogP) favor the inhibitory effect of these colorings toward both enzymes. Also, a negative role of the number of heavy atoms has been demonstrated in the phenomenon of inhibition of this enzyme. Finally, the descriptor εlumo (electronic affinity) plays a crucial role on the inhibitory power of these dyes toward both enzymes by electron transfer. The virtual screening of the inhibition of α-amylase and α-glucosidase by these colorings, using Molegro Virtual Docker (MVD), allowed us to obtain stable complexes with interaction energies resulting from the place of hydrogen bonds and several hydrophobic interactions. However, the sulfonate groups of these colorings can be the major factors in the inhibition of these enzymes. On the other hand, Rerank Score with the pose are perfectly correlated (R2> 0.76) to the inhibitory activity of these food colorings measured experimentally. Conclusion: The present study suggests that the Blue Patent V (SIN131) effectively act as α-amylase and α-glucosidase inhibitor leading to a reduction in starch hydrolysis and hence eventually to lowered glucose levels.

In vitro and in silico studies on AChE inhibitory effects of a series of donepezil-like arylidene indanones

2020 ◽  
Vol 45 (4) ◽  
pp. 359-363
Author(s):  
Belgin Sever ◽  
Mehlika Dilek Altıntop ◽  
Halide Edip Temel
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Ache Inhibitor ◽  
Ache Inhibition ◽  
Lipinski’S Rule ◽  
In Silico Studies ◽  
Orally Bioavailable

AbstractObjectiveDonepezil is the most potent acetylcholinesterase (AChE) inhibitor currently available on the market for the management of Alzheimer’s disease. In this study, it was aimed to identify potent donepezil analogues.Materials and methodsThe effects of arylidene indanones (1–10) on AChE inhibition were examined using modified Ellman’s assay. Compound 4, the most potent arylidene indanone in this series, was subjected to molecular docking to anticipate its binding mode in the AChE site (PDB code: 4EY7). The pharmacokinetic profiles of all derivatives were also predicted.ResultsCompound 4 was found as the most potent AChE inhibitor with an IC50 value of 5.93 ± 0.29 μg/mL. According to molecular docking studies, compound 4 presented favorable interactions such as π–π interactions with Trp286 and Tyr337. In silico studies revealed that the compound did not violate Lipinski’s rule of five and Jorgensen’s rule of three, making it a potential orally bioavailable agent.ConclusionCompound 4 is a feasible candidate for further experiments related to AChE inhibition.

scholarly journals In Vitro and In Silico Acetylcholinesterase Inhibitory Activity of Thalictricavine and Canadine and Their Predicted Penetration across the Blood-Brain Barrier

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1340 ◽  
Author(s):  
Jakub Chlebek ◽  
Jan Korábečný ◽  
Rafael Doležal ◽  
Šárka Štěpánková ◽  
Daniel Pérez ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Binding Mode ◽  
Brain Barrier ◽  
In Silico Docking ◽  
Lead Compounds ◽  
Blood Brain ◽  
Type Pattern ◽  
Ic50 Values

In recent studies, several alkaloids acting as cholinesterase inhibitors were isolated from Corydalis cava (Papaveraceae). Inhibitory activities of (+)-thalictricavine (1) and (+)-canadine (2) on human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) were evaluated with the Ellman’s spectrophotometric method. Molecular modeling was used to inspect the binding mode of compounds into the active site pocket of hAChE. The possible permeability of 1 and 2 through the blood–brain barrier (BBB) was predicted by the parallel artificial permeation assay (PAMPA) and logBB calculation. In vitro, 1 and 2 were found to be selective hAChE inhibitors with IC50 values of 0.38 ± 0.05 µM and 0.70 ± 0.07 µM, respectively, but against hBChE were considered inactive (IC50 values > 100 µM). Furthermore, both alkaloids demonstrated a competitive-type pattern of hAChE inhibition and bind, most probably, in the same AChE sub-site as its substrate. In silico docking experiments allowed us to confirm their binding poses into the active center of hAChE. Based on the PAMPA and logBB calculation, 2 is potentially centrally active, but for 1 BBB crossing is limited. In conclusion, 1 and 2 appear as potential lead compounds for the treatment of Alzheimer’s disease.

scholarly journals Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from Boswellia elongata with Structure-Activity Relationship: In Vitro and In Silico Studies

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 751 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Sobia Ahsan Halim ◽  
Mohammed Al-Azri ◽  
Majid Khan ◽  
Ajmal Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Dissociation Constants ◽  
Docking Study ◽  
Spectroscopic Techniques ◽  
Significant Activity ◽  
Active Compounds ◽  
In Silico Docking ◽  
In Silico Studies ◽  
First Time

Fourteen triterpene acids, viz., three tirucallane-type (1–3), eight ursane-type (4–11), two oleanane-type (12, 13) and one lupane type (21), along with boswellic aldehyde (14), α-amyrine (15), epi-amyrine (16), straight chain acid (17), sesquiterpene (19) and two cembrane-type diterpenes (18, 20) were isolated, first time, from the methanol extract of Boswellia elongata resin. Compound (1) was isolated for first time as a natural product, while the remaining compounds (2‒21) were reported for first time from B. elongata. The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (1–5, 11, 19 and 20) were further screened for in vitro α-glucosidase inhibitory activity. Compounds 3–5 and 11 showed significant activity against α-glucosidase with IC50 values ranging from 9.9–56.8 μM. Compound 4 (IC50 = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by 11 (IC50 = 14.9 ± 1.31 μM), 5 (IC50 = 20.9 ± 0.05 μM) and 3 (IC50 = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds 3–5 and 11 were carried out to investigate their mechanism (mode of inhibition and dissociation constants Ki). All compounds were found to be non-competitive inhibitors with Ki values in the range of 7.05 ± 0.17–51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

2020 ◽  
Vol 16 ◽  
Author(s):  
Mahboob Ali ◽  
Momin Khan ◽  
Khair Zaman ◽  
Abdul Wadood ◽  
Maryam Iqbal ◽  
...  
Keyword(s):  
In Silico ◽  
Enzyme Inhibitors ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Type Ii Diabetes Mellitus ◽  
Spectroscopic Techniques ◽  
Chalcone Derivatives ◽  
In Silico Studies ◽  
Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

scholarly journals Synthesis, Characterization, in vitro Antimicrobial Evaluation and in silico Molecular Docking and ADME Prediction of 4-Chlorophenyl Furfuran Derivatives bearing Pyrazole Moieties

2020 ◽  
Vol 32 (6) ◽  
pp. 1482-1490
Author(s):  
Manju Mathew ◽  
Raja Chinnamanayakar ◽  
Ezhilarasi Muthuvel Ramanathan
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Docking Studies ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Adme Prediction ◽  
Antimicrobial Studies ◽  
In Silico Molecular Docking

A series of 1-(5-(5-(4-chlorophenyl)furan-2-yl)-4,5-dihyropyrazol-1-yl ethanone (5a-h) was synthesized through E-(3-(5-(4-chloro-phenyl)furan-2-yl)-1-phenylprop-2-en-1-one (3a-h) with hydrazine monohydrate and sodium acetate. Totally, eight compounds were synthesized and their structures were elucidated by infrared, 1H & 13C NMR, elemental analysis, antimicrobial studies, in silico molecular docking studies and also in silico ADME prediction. Antimicrobial studies of the synthesized compounds showed good to moderate activity against the all the stains compared with standard drugs. in silico Molecular docking study was carried out using bacterial protein and BC protein. Synthesized compounds (5a-h) showed good docking score compared with ciprofloxacin. Antimicrobial study was carried out for 4-chlorophenyl furfuran pyrazole derivatives (5a-h). The results of assessment of toxicities, drug likeness and drug score profiles of compounds (5a-j) are promising

scholarly journals Oleuropein modulates over-proliferation of keratinocytes in mice with imiquimodmediated psoriasis and inhibits differentiation of TH17 cells through the JAK3/STAT3 axis

2020 ◽  
Author(s):  
Quan Shi ◽  
Qi He ◽  
Weiming Chen ◽  
Jianwen Long ◽  
Bo Zhang
Keyword(s):  
T Cells ◽  
In Silico ◽  
Th17 Cells ◽  
Skin Lesions ◽  
Docking Studies ◽  
Inflammatory Disorder ◽  
T Helper 17 ◽  
In Silico Docking

IntroductionOleuropein (OLP) is polyphenol obtained from olive oil; it is proved in Chinese traditional medicine for its use in disorders including autoimmune and inflammatory disorders. Psoriasis (PSR) is an autoimmune and inflammatory disorder triggered by T-helper-17 (Th17) cells.Material and methodsWe developed an imiquimod (IMQ)-mediated PSR model in mice to study the anti-inflammatory role of OLP in psoriasis. The mice were given 50 mg/kg and 100 mg/kg dose of OLP. Histology was done to assess the inflammation of lesions. Western blot analysis was done for JAK3/STAT3 in isolated T cells, expression of RORgt was done by RT-PCR. The In silico molecular docking studies were done for interaction of OLP with target protein STAT3 and JAK3.ResultsTreatment of OLP attenuated proliferation in IMQ-mediated keratinocytes, improved infiltration of CD3+ cells in the skin lesions and in CD4+ and CD8+ T cells and also ameliorated the levels of cytokines. In in vitro studies in isolated T cells, OLP blocked the differentiation of Th17 cells and also the levels of IL-17 and the JAK3/STAT3 pathway. The in silico docking showed that OLP had potential binding affinity with JAK3 and STAT3 which was parallel to in vivo and in vitro findings.ConclusionsOLP ameliorates psoriasis skin lesions by blocking Th17-mediated inflammation. OLP may be an interesting molecule for treating autoimmunity in psoriasis.

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