Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of Novel Triazinoindole-Based Thiourea Hybrid: A Study on ?-Glucosidase Inhibitors and Their Molecular Docking.

ABSTRACT: A new class of triazinoindole-bearing thiosemicarbazides (1-25) was synthesized and evaluated for ?-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared to standard acarbose (an IC50 value of 38.60 ± 0.20 µM). Among the series, analogs 1 and 23 were found to be the most potent, with IC50 values of 1.30 ± 0.05 and 1.30 ± 0.01 µM, respectively. The structure-activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.

SUBMITTER: Taha M

PROVIDER: S-EPMC6864627 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of Novel Triazinoindole-Based Thiourea Hybrid: A Study on α-Glucosidase Inhibitors and Their Molecular Docking.

Taha Muhammad M Alshamrani Foziah J FJ Rahim Fazal F Hayat Shawkat S Ullah Hayat H Zaman Khalid K Imran Syahrul S Khan Khalid Mohammed KM Naz Farzana F

Molecules (Basel, Switzerland) 20191023 21

A new class of triazinoindole-bearing thiosemicarbazides (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared to standard acarbose (an IC50 value of 38.60 ± 0.20 µM). Among the series, analogs 1 and 23 were found to be the most potent, with IC50 values of 1.30 ± 0.05 and 1. ...[more]

PMID: 31652777

Similar Datasets

Synthesis of novel coumarin-hydrazone hybrids as α-glucosidase inhibitors and their molecular docking studies.

Project description:Diabetes mellitus is a metabolic disorder and more than 90% of diabetic patients suffer from type-2 diabetes, which is characterized by hyperglycemia. α-Glucosidase inhibition has become an appropriate approach to tackle high blood glucose levels. The current study was focused on synthesizing coumarin-hydrazone hybrids (7a-i) by using facile chemical reactions. The synthesized compounds were characterized by using 1H-NMR, 13C-NMR, and IR. To evaluate their anti-diabetic capability, all of the conjugates were screened for in vitro α-glucosidase inhibitory activity to reveal their therapeutic importance. All of the compounds (except 7b) demonstrated significant enzyme inhibitory potential with IC50 values ranging between 2.39-57.52 μM, as compared to the standard inhibitor, acarbose (IC50 = 873.34 ± 1.67 μM). Among them, compound 7c is the most potent α-glucosidase inhibitor (IC50 = 2.39 ± 0.05 μM). Additionally, molecular docking was employed to scrutinize the binding pattern of active compounds within the α-glucosidase binding site. The in silico analysis reflects that hydrazone moiety is an essential pharmacophore for the binding of compounds with the active site residues of the enzyme. This study demonstrates that compounds 7c and 7f deserve further molecular optimization for potential application in diabetic management.

| S-EPMC10475976 | biostudies-literature

Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin-Thiazole Derivatives as α-Glucosidase Inhibitors.

Project description:A series of novel isatin-thiazole derivatives were synthesized and screened for their in vitro α-glucosidase inhibitory activity. These compounds displayed a varying degree of α-glucosidase inhibitory activity with IC50 ranging from 5.36 ± 0.13 to 35.76 ± 0.31 μm as compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μm). Among the series, compound 6p bearing a hydroxyl group at the 4-position of the right phenyl and 2-fluorobenzyl substituent at the N1-positions of the 5-methylisatin displayed the highest inhibitory activity with an IC50 value of 5.36 ± 0.13 μm. Molecular docking studies revealed the existence of hydrophobic interaction, CH-π interaction, arene-anion interaction, arene-cation interaction, and hydrogen bond between these compounds and α-glucosidase enzyme.

| S-EPMC6154535 | biostudies-literature

Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics.

Project description:A series of symmetrical salicylaldehyde-bishydrazine azo molecules, 5a-5h, have been synthesized, characterized by 1H-NMR and 13C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound 5g was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase. The IC50 of 5g against α-glucosidase was 0.35917 ± 0.0189 µM (standard acarbose IC50 = 6.109 ± 0.329 µM), and the IC50 value of 5g against α-amylase was 0.4379 ± 0.0423 µM (standard acarbose IC50 = 33.178 ± 2.392 µM). The Lineweaver-Burk plot indicated that compound 5g is a competitive inhibitor of α-glucosidase. The binding interactions of the most active analogues were confirmed through molecular docking studies. Docking studies showed that 5g interacts with the residues Trp690, Asp548, Arg425, and Glu426, which form hydrogen bonds to 5g with distances of 2.05, 2.20, 2.10 and 2.18 Å, respectively. All compounds showed high mutagenic and tumorigenic behaviors, and only 5e showed irritant properties. In addition, all the derivatives showed good antioxidant activities. The pharmacokinetic evaluation also revealed promising results.

| S-EPMC6515238 | biostudies-literature

Synthesis of Novel Benzimidazole-Based Thiazole Derivatives as Multipotent Inhibitors of α-Amylase and α-Glucosidase: In Vitro Evaluation along with Molecular Docking Study.

Project description:In this study, hybrid analogs of benzimidazole containing a thiazole moiety (1-17) were afforded and then tested for their ability to inhibit α-amylase and α-glucosidase when compared to acarbose as a standard drug. The recently available analogs showed a wide variety of inhibitory potentials that ranged between 1.31 ± 0.05 and 38.60 ± 0.70 µM (against α-amylase) and between 2.71 ± 0.10 and 42.31 ± 0.70 µM (against α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM against α-amylase) (IC50 = 9.80 ± 0.20 µM against α-glucosidase). A structure-activity relationship (SAR) study was carried out for all analogs based on substitution patterns around both rings B and C respectively. It was concluded from the SAR study that analogs bearing either substituent(s) of smaller size (-F and Cl) or substituent(s) capable of forming hydrogen bonding (-OH) with the catalytic residues of targeted enzymes enhanced the inhibitory potentials. Therefore, analogs 2 (bearing meta-fluoro substitution), 3 (having para-fluoro substitution) and 4 (with ortho-fluoro group) showed enhanced potency when evaluated against standard acarbose drug with IC50 values of 4.10 ± 0.10, 1.30 ± 0.05 and 1.90 ± 0.10 (against α-amylase) and 5.60 ± 0.10, 2.70 ± 0.10 and 2.90 ± 0.10 µM (against α-glucosidase), correspondingly. On the other hand, analogs bearing substituent(s) of either a bulky nature (-Br) or that are incapable of forming hydrogen bonds (-CH3) were found to lower the inhibitory potentials. In order to investigate the binding sites for synthetic analogs and how they interact with the active areas of both targeted enzymes, molecular docking studies were also conducted on the potent analogs. The results showed that these analogs adopted many important interactions with the active areas of enzymes. The precise structure of the newly synthesized compounds was confirmed using several spectroscopic techniques as NMR and HREI-MS.

| S-EPMC9572811 | biostudies-literature

Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors.

Project description:Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC50 of 104.07 µM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand-α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329.25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids have been synthesized and evaluated their α-glucosidase inhibitory activity. Compounds 6h have shown stronger activity than that of acarbose.

| S-EPMC6661812 | biostudies-literature

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors.

Project description:Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure-activity relationship, attaching 4-bromobutoxy or 4'-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and 10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.

| S-EPMC10222686 | biostudies-literature

Synthesis, Biological Evaluation and Molecular Docking Study of 2-Substituted-4,6-Diarylpyrimidines as α-Glucosidase Inhibitors.

Project description:A novel series of 2-substituted-4,6-diarylpyrimidines 6a-6t has been synthesized, characterized by ¹H-NMR, 13C-NMR and HRMS, and screened for in vitro α-glucosidase inhibitory activity. The majority of the screened compounds possessed significant α-glucosidase inhibitory activity with IC50 values ranging from 19.6 ± 0.21 to 38.9 ± 0.35 μM, which is more potent than the positive control α-glucosidase inhibitor acarbose (IC50 = 817.38 ± 6.27 μM). Among them, 6j was found to be the most active compound against α-glucosidase with an IC50 of 19.6 ± 0.21 μM. In addition, molecular docking studies were carried out to explore the binding interactions of 2-substituted-4,6-diarylpyrimidine derivatives with α-glucosidase.

| S-EPMC6150375 | biostudies-literature

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors.

Project description:A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a-o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a-o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results.

| S-EPMC9341091 | biostudies-literature

Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study.

Project description:Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (7-21) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives 19 (IC50 = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and 20 (IC50 = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC50 = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure-activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes.

| S-EPMC9609971 | biostudies-literature

Synthesis, In Vitro α-Glucosidase Inhibitory Activity and Molecular Docking Studies of Novel Benzothiazole-Triazole Derivatives.

Project description:Benzothiazole-triazole derivatives 6a-6s have been synthesized and characterized by ¹HNMR and 13C-NMR. All synthetic compounds were screened for their in vitro α-glucosidase inhibitory activity by using Baker's yeast α-glucosidase enzyme. The majority of compounds exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 20.7 and 61.1 μM when compared with standard acarbose (IC50 = 817.38 μM). Among the series, compound 6s (IC50 = 20.7 μM) bearing a chlorine group at the 5-position of the benzothiazole ring and a tertbutyl group at the para position of the phenyl ring, was found to be the most active compound. Preliminary structure-activity relationships were established. Molecular docking studies were performed to predict the binding interaction of the compounds in the binding pocket of the enzyme.

| S-EPMC6151782 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data