Synthesis, molecular docking and QSAR study of thiazole clubbed pyrazole hybrid as α-amylase inhibitor

Duhan, Meenakshi; Singh, Rahul; Devi, Meena; Sindhu, Jayant; Bhatia, Rimpy; Kumar, Ashwani; Kumar, Parvin

doi:10.1080/07391102.2019.1704885

Cited by 61 publications

(30 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By comparing the structures and activities of the synthesized molecules, compounds 3b-d, halogenated in the para position of the phenyl group attached to the isoxazole ring, displayed significant efficacy (PI= 85.4 ± 0.9%-94.7 ± 1.2%at 50 µM) and potency (IC 50 = 12.6 ± 0.2 µM-14.6 ± 0.3 µM) in inhibiting the α-amylase enzyme. This finding is in good agreement with the literature, showing that the presence of halogen atoms (F, Cl, or Br) in the structure was essential for a potent α-amylase inhibition [49,50]. In addition, the structure-activity relationship study allowed us to conclude that more inductive attractor (−I) and mesomeric donor (+M) effects increase the α-amylase inhibitory efficacy and potency (activity of the fluorinated derivative 3b (R 1 = F, R 2 = H; PI = 94.7 ± 1.2% at 50 µM; IC 50 = 12.6 ± 0.2 µM) is higher than that of the chlorinated derivative 3c (R 1 = Cl, R 2 = H; PI = 87.1 ± 0.7% at 50 µM; IC 50 = 14.4 ± 0.2 µM), followed by the brominated derivative 3d (R 1 = Br, R 2 = H; PI = 85.4 ± 0.9% at 50 µM; IC 50 = 14.6 ± 0.3 µM)), in accordance with previous studies [4,49].…”

Section: Valuation Of α-Amylase Inhibitionsupporting

confidence: 92%

“…One review of the literature mentions that trifluoromethylated 5-amino-nicotinic acid has been reported to exhibit promising α-amylase activity [49]. In addition, the chlorinated hybrid pyrazole-thiazole molecules were found to be good inhibitors of the α-amylase enzyme [50], which also indicates the importance of the chlorine atom in α-amylase inhibitory structures.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure–Activity Relationship Analysis

et al. 2021

View full text Add to dashboard Cite

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by 1H NMR, 13C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 μM, and with IC50 values of 12.6 ± 0.2 μM–27.6 ± 1.1 μM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 μM), with a potency (IC50 = 12.6 ± 0.2 μM) similar to that of the positive control acarbose (IC50 = 12.4 ± 0.1 μM). The study of the structure–activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.

show abstract

Section: Valuation Of α-Amylase Inhibitionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure–Activity Relationship Analysis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Notably, compound 5 emerged as PPAR-γ and antiamylase agent [29] and 6 as a potent α-amylase inhibitor (Figure 1). [30] Hence, the incorporation of the pyrazole motif in the design of drug candidates could enhance the biological profile.…”

mentioning

confidence: 99%

In vitro and in silico studies of fluorinated 2,3‐disubstituted thiazolidinone‐pyrazoles as potential α‐amylase inhibitors and antioxidant agents

Ganavi

Ramu

Kumar

et al. 2021

Archiv der Pharmazie

View full text Add to dashboard Cite

As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their αamylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC 50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC 50 = 0.86 ± 0.81 μM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK).

show abstract

“…[20][21][22][23] In recent times, many publications utilized the 'index of ideality of correlation (IIC)' as a unique criterion to construct the best predictive QSPR models. [24][25][26][27] The goal of the present study is to construct the QSPR models based on a hybrid optimal descriptor obtained from SMILES and a hydrogen-suppressed graph (HSG) to predict the T m for a dataset of 353 imidazolium ILs. The index of ideality of correlation (IIC) is assessed as a criterion of predictive potential of the QSPR models of T m .…”

Section: Introductionmentioning

confidence: 99%

The Monte Carlo approach to model and predict the melting point of imidazolium ionic liquids using hybrid optimal descriptors

2021

Self Cite

View full text Add to dashboard Cite

show abstract

Synthesis, molecular docking and QSAR study of thiazole clubbed pyrazole hybrid as α-amylase inhibitor

Cited by 61 publications

References 85 publications

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure–Activity Relationship Analysis

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure–Activity Relationship Analysis

In vitro and in silico studies of fluorinated 2,3‐disubstituted thiazolidinone‐pyrazoles as potential α‐amylase inhibitors and antioxidant agents

The Monte Carlo approach to model and predict the melting point of imidazolium ionic liquids using hybrid optimal descriptors

Contact Info

Product

Resources

About