Novel benzoxazole derivatives featuring rhodanine and analogs as antihypergycemic agents: synthesis, molecular docking, and biological studies

Gatphoh

et al. 2021

Preprint

In search for possible antidiabetic agents, a new series of Benzothiazole-Rhodanine derivatives (A1-10) have been synthesized and characterized by spectral data(IR, 1H-NMR, C13-NMR,and HR-MS).All the designed compounds were subjected to In-silico studies using Schrodinger softwareand evaluated for In-vitro antidiabetic activityby α-amylase and α-glucosidase inhibitory assays.Among the tested compoundsA5, A6 and A9 showed good activity when compared to the standard Acarbose. Also, Molecular dynamic (MD) simulations were conducted to evaluate the stability of the ligand-protein complex by the calculation of the root mean of square deviation (RMSD), root mean square fluctuation (RMSF), and solvent accessible surface area (SASA).

Section: Chemistrymentioning

confidence: 78%

Identification of Benzothiazole‒Rhodanine Derivatives as α-Amylase and α-Glucosidase Inhibitors: Design, Synthesis, In-silico and In-Vitro Analysis

Sriniv

Gatphoh

et al. 2021

Preprint

“…Qikprop gives the information of different molecular descriptors, for example, SASA, MW, dipole, PISA, PSA, FOSA, FISA, #rotor, volume, QPpolrz, QPlogPo/w, QPLogKhsa, QPlogBB, donor HB, accept HB, to decide #star boundary. #star values in the range of <5, helps to conclude that the synthesized compounds have similar properties to the known drugs[17] Table-6.…”

mentioning

confidence: 69%

“…i Predicted percentage human absorption.Qikprop gives the information of different molecular descriptors, for example, SASA, MW, dipole, PISA, PSA, FOSA, FISA, #rotor, volume, QPpolrz, QPlogPo/w, QPLogKhsa, QPlogBB, donor HB, accept HB, to decide #star boundary. #star values in the range of <5, helps to conclude that the synthesized compounds have similar properties to the known drugs[17] Table-6.a Number of reactive functional groups b Total solvent accessible surface area c FOSA :Hydrophobic component of the SASA (saturated carbon and attached hydrogen). d FISA: Hydrophilic component of the SASA (SASA on N, O, and H on heteroatoms).…”

mentioning

confidence: 89%

Identification of Benzothiazole‒Rhodanine Derivatives as α-Amylase and α-Glucosidase Inhibitors: Design, Synthesis, In-silico and In-Vitro Analysis

Srinivasa

Gatphoh

et al. 2021

Preprint

In search for possible antidiabetic agents, a new series of Benzothiazole-Rhodanine derivatives (A1-10) have been synthesized and characterized by spectral data (IR, 1 H-NMR, C 13 -NMR, and HR-MS). All the designed compounds were subjected to In-silico studies using Schrodinger software and evaluated for In-vitro antidiabetic activity by α-amylase and α-glucosidase inhibitory assays. Among the tested compounds A5, A6 and A9 showed good activity when compared to the standard Acarbose. Also, Molecular dynamic (MD) simulations were conducted to evaluate the stability of the ligand-protein complex by the calculation of the root mean of square deviation (RMSD), root mean square fluctuation (RMSF), and solvent accessible surface area (SASA).

“…According to the docking study, observed in acarbose most of the hydrogen bond interaction were observed with hydroxyl group (Figure 3). Among the synthesized compounds A5 and A9 also showed hydrogen bond interaction with hydroxyl group, so electron‐donating groups shows better inhibitory activity 27 …”

Section: Resultsmentioning

confidence: 99%

“…Among the synthesized compounds A5 and A9 also showed hydrogen bond interaction with hydroxyl group, so electron-donating groups shows better inhibitory activity. 27…”

Section: Kinetic Study Of α-Amylase and α-Glucosidasementioning

confidence: 99%

Identification of benzothiazole‐rhodanine derivatives as α‐amylase and α‐glucosidase inhibitors: Design, synthesis, in silico, and in vitro analysis

Srinivasa

J of Molecular Recognition

Gatpoh

et al. 2022

A novel series of benzothiazole-rhodanine derivatives (A1-A10) were designed and synthesized, with the aim of developing possible antidiabetic agents and the spectral characterization of these compounds was done using infrared spectroscopy (IR), proton-nuclear magnetic resonance ( 1 H-NMR), carbon-nuclear magnetic resonance (C 13 -NMR), and high resolution mass spectroscopy (HR-MS) techniques. In vitro hypoglycemic potential of the compounds was evaluated by performing α-amylase and α-glucosidase enzyme inhibitory assays. In addition, these compounds were subjected to in silico analysis. Based on the results, compounds A5, A6, and A9 displayed good activity in comparison with the standard acarbose. Based on Lineweaver-Burk plots, it was concluded that compounds A5 and A9 displayed competitive type of enzyme inhibition. Molecular dynamic simulations were conducted to evaluate the stability of the ligand-protein complex by the calculation of the root mean square deviation, root means square fluctuation, and solvent accessible surface area.diabetes mellitus, in silico analysis, molecular dynamics, pharmacophore, rhodanines | INTRODUCTIONDiabetes mellitus (DM) is a chronic metabolic disorder that causes a significant challenge for the healthcare system across the globe. Such a high prevalence of diabetes has boosted the search for novel alternatives. Owing to high blood glucose in diabetes, a series of complications such as blindness, high blood pressure, kidney, and stroke disorders may result. 1 Diabetes was anticipated to affect 415 million people in 2015, with type 2 diabetes (T2DM) accounting for more than 90% of cases, with the number expected to rise to 642 million by 2040. For controlling glycemia, there has been a development of a few synthetic drugs such as acarbose, metformin, and sitagliptin. However, many side effects have been resulted due to the consumption of these drugs, such as flatulence, diarrhea, and hypoglycemia. It is well-known that postprandial hyperglycemia is an important contributing factor to the progression of T2DM, therefore, postprandial management of hyperglycemia is one of the therapeutic approaches to combating T2DM diabetes. α-amylase and α-glucosidase are the two main carbohydrate digestive enzymes associated with postprandial hyperglycemia in T2DM patients. The alpha-1, 4-glycosidic bond