Synthesis and molecular docking studies of 5-acetyl-2-(arylidenehydrazin-1-yl)-4-methyl-1,3-thiazoles as α-amylase inhibitors

Mehmood, Hasnain; Haroon, Muhammad; Akhtar, Tashfeen; Woodward, Simon; Andleeb, Hina

doi:10.1016/j.molstruc.2021.131807

Cited by 13 publications

(14 citation statements)

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“…The results showed in [56][57][58][59]. The results confirms that redocked acarbose mimic the binding pattern of reference inhibitor that is acarbose co-crystallized with target protein (Table 3, Fig.…”

Section: Binding Score Analysissupporting

confidence: 70%

Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Dukhyil

2021

JPRI

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Aims: Diabetes mellitus (DM) is chronic disorder well known for increased glucose level in blood. This disease can be controlled by inhibiting the enzyme (e.g., α-amylase) involve in carbohydrate hydrolysis. Senna auriculata leaves methanolic extract (SALME) have potential antidiabetic properties and it was also found to be safe in preclinical studies. In this study the aim was to explore the molecular interactions of α-amylase and bioactive compounds in SALME and their physicochemical properties. Methodology: Computational approach such as molecular docking and physicochemical analysis prediction was applied to understand the antidiabetic potential of natural compounds present in SALME. Results: The results showed from physicochemical analysis that out of 11 only 7 compounds are having drug like properties which are orally and intestinally better bioavailable. Furthermore, molecular docking analysis explained that three compounds (C3, C4, and C7) have lower binding energy, ΔG (-8, -9.1, -9.5 kcal/mol) and better binding affinity, Ki (7.31 x 105, 4.68 x 106, and 9.2 x 106 M-1, respectively) than the acarbose ΔG (-7.8 kcal/mol) and Ki (6.18 x 105 M-1), a well-known FDA approved medication for DM. The study also explained the binding pattern that the catalytic residue such as Asp197, Glu233 and Asp300 are involved in stabilizing the natural compounds with in the catalytic active site of target enzyme. Conclusions: From the results it has been concluded that these three compounds found in SALME have better inhibitory potential for α-amylase in comparison with acarbose. Further validation of the findings is required through molecular dynamics simulation, ADME-T study, and in-vitro enzyme inhibition by the purified compounds.

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Section: Binding Score Analysissupporting

confidence: 70%

Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Dukhyil

2021

JPRI

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“…A library of 30 compounds was prepared using a-bromo-4cyanoacetophenone (2, R 1 = 4-C 6 H 4 CN in all cases) from a range of readily available thiosemicarbazones (1a-d ′ ). [17][18][19][20][21][22][23][24][25] Reux of the reaction components in ethanol for 3-3.5 h afforded modest to good yields of 3a-d ′ (Table 1) all of which could be isolated by simple ltration of directly precipitated products.…”

Section: Synthesis Of 4-substituted 2-hydrazinylthiazole Species (3)mentioning

confidence: 99%

“…Initial thiosemicarbazones (1) are readily available either commercially and via simple one-step literature procedures (see ref. [17][18][19][20][21][22][23][24][25]. Chromatographic silica gel 60 (220-240 mesh) was obtained from Merck.…”

Section: Generalmentioning

confidence: 99%

“…[14][15][16] Although the compounds 4 suggest a clear (anti-cancer) benet from 4-cyanophenyl inclusion within the 2-hydrazinylthiazole derivative 4, this series was synthetically problematic to work with. Therefore, as part of our ongoing research, 17 we set out to synthesise a range of more simply and easily accessed 2-hydrazinylthiazole species (3), all bearing a cyanoaryl moiety at position R 1 (Scheme 1), to conrm the generality of the apparent activity effect detected.…”

Section: Introductionmentioning

confidence: 99%

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Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

et al. 2022

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“…Compounds I and II (Figure ) were highlighted as excellent antiglycating agents with IC 50 values of 1.848 ± 0.646 and 0.0004 ± 1.097 μM, respectively (amino guanidine, IC 50 = 25.50 ± 0.337 μM). In addition, Hasnain et al reported the syntheses of two series of hydrazinylthiazoles and evaluated their antiglycation and α-amylase inhibition potential. , Compounds III and IV (Figure ) were found to be potential α-amylase inhibitors with IC 50 values of 4.80 ± 0.07 and 4.79 ± 0.08 μM, respectively (acarbose, IC 50 = 5.62 ± 0.04 μM). They also reported compound V as an excellent antiglycating agent with IC 50 value of 0.383 ± 0.001 mg/mL as compared to the standard amino guanidine (IC 50 = 0.394 ± 0.001 mg/mL).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management

et al. 2023

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A novel series of fluorophenyl-based thiazoles was synthesized following the Hanztsch method. All of the compounds were initially verified with physical parameters (color, melting point, retardation factor (R f)), which were further confirmed by several spectroscopic methods, including ultraviolet–visible (UV–visible), Fourier-transform infrared (FTIR), 1H, 13C, 19F NMR, and high-resolution mass spectrometry (HRMS). The binding interactions of all compounds were studied using a molecular docking simulation approach. Furthermore, each compound was evaluated for its alpha(α)-amylase, antiglycation, and antioxidant potentials. The biocompatibility of all compounds was checked with an in vitro hemolytic assay. All synthesized scaffolds were found biocompatible with minimal lysis of human erythrocytes as compared to the standard Triton X-100. Among the tested compounds, the analogue 3h (IC50 = 5.14 ± 0.03 μM) was found to be a highly potent candidate against α-amylase as compared to the standard (acarbose, IC50 = 5.55 ± 0.06 μM). The compounds 3d, 3f, 3i, and 3k exhibited excellent antiglycation inhibition potential with their IC50 values far less than the standard amino guanidine (IC50 = 0.403 ± 0.001 mg/mL). The antidiabetic potential was further supported by docking studies. Docking studies revealed that all synthesized compounds exhibited various interactions along enzyme active sites (pi–pi, H-bonding, van der Waals) with varied binding energies.

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Synthesis and molecular docking studies of 5-acetyl-2-(arylidenehydrazin-1-yl)-4-methyl-1,3-thiazoles as α-amylase inhibitors

Cited by 13 publications

References 50 publications

Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management

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