Synthesis, in vitro biological analysis and molecular docking studies of new thiadiazole-based thiourea derivatives as dual inhibitors of a-amylase and a-glucosidase

Khan, Imran; Rehman, Wajid; Hussain, Rafaqat; Khan, Shoaib; Rasheed, Liaqat; Alanazi, Ashwag S.; Hefnawy, Mohamed M.; Alanazi, Mohammed M.; Taha, Muhammad

doi:10.1016/j.arabjc.2023.105078

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…Then, an equimolor amount of intermediate ( II ) and varied substituted phenacyl bromide were mixed and stirred for about 6 hrs in ethanol (10 mL) followed by catalytic addition of ET 3 N to obtain bis‐indole‐based triazine substrate ( III) . This work was previously done by our research group [38,39] . In the next step, an intermediate ( III , 1 mmol) was treated with thiosemicarbazide (1 mmol) in glacial acetic acid (10 mL) to afford thiosemicarbazone intermediate (IV) which further underwent cyclization on treating with chloro acetic acid (1 mmol) in glacial acetic acid (10 mL) and sodium acetate (catalyst) under reflux condition for about 6 hrs, afforded bis ‐indole‐derived triazine based thiazolidinone derivatives ( 1 – 12 ) in appropriate yield (scheme 1).…”

Section: Methodsmentioning

confidence: 99%

Developing Correlation Between In Silico Molecular Modeling and In Vitro α‐Amylase, Anti‐Cancer and SARS‐COV‐2 Studies of Bis‐Indole Derived Triazine‐Based Thiazolidinone Hybrid Derivatives

Khan,

Hussain,

Khan

et al. 2024

ChemistrySelect

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In the era of COVID‐19 most of the marketed drugs have been found with some negative effects as well as with fewer numbers in the market. There is a serious need of an anti‐COVID agent which can maintain the normal body function with fewer or no side effects. For this purpose, hybrid derivatives based on bis‐indole derived triazine based thiazolidinone derivatives (1–12) were successfully synthesized and characterized using various spectroscopic techniques including 1H NMR, 13C NMR and HREI‐MS. All the synthesized bis‐indole derived triazine‐bearing thiazolidinone derivatives were tested for in vitro α‐amylase, cancer cell and SARS‐COV‐2 enzymes under the positive control of Acarbose, Tetrandrine and GC‐376 as standard drugs. All derivatives showed varied range of biological activities against target enzymes having IC50 values ranging from 3.10±0.20 to 25.80±0.20 μM (α‐amylase), 0.20±0.30 to 19.10±0.20 μM (ant‐cancer) and 3.20±0.20 to 16.20±0.30 μM (SARS‐COV‐2), respectively. Specifically, derivatives 1, 3, 6, 8 and 9 were found to significantly active against target enzymes. Furthermore, the molecular docking approach was used to explore the binding interactions established by most active derivatives with the active sites of target enzymes and results corroborated that these active compounds developed several key interactions with the target enzymes and hence enhanced the enzymatic activities. Additionally, ADME prediction for the synthesized compounds were also explored which shows drug likeness of the synthesized compounds.

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Section: Methodsmentioning

confidence: 99%

Developing Correlation Between In Silico Molecular Modeling and In Vitro α‐Amylase, Anti‐Cancer and SARS‐COV‐2 Studies of Bis‐Indole Derived Triazine‐Based Thiazolidinone Hybrid Derivatives

Khan,

Hussain,

Khan

et al. 2024

ChemistrySelect

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“…These compounds, namely urea, [15] thiourea, [16,17] and thiosemicarbazide [16] have been scrutinized as antidiabetic agents (Figure 1), a facet in which their efficacy akin to urea stands out. From last year until now, many urea derivatives and their analogs have been synthesized, including nimesulide-linked acyl thioureas, [18] benzimidazole ureas, [19] arylureidoaurones, [20] thioureas based on thiadiazole, [21] benzimidazole thiosemicarbazones, [1] and chromone-derived thiosemicarbazones [22] all of which have been proven to be potential α-glucosidase inhibitors for diabetes treatment. In a similar vein, a new series of urea analog known as carbonylbis(hydrazine-1carbothioamide has been introduced.…”

Section: Introductionmentioning

confidence: 99%

Carbonylbis(hydrazine‐1‐carbothioamide) derivatives as a new class of α‐glucosidase inhibitors and their mechanistic insights via molecular docking and dynamic simulations

Naseem,

Fatima,

Ullah

et al. 2023

Archiv der Pharmazie

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In the past, efforts have been made to find a cure for diabetes, mainly evaluating new classes of compounds to explore their potency. In this study, we present the synthesis and evaluation of carbonylbis(hydrazine‐1‐carbothioamide) derivatives as potential α‐glucosidase inhibitors, employing both in vivo and in silico investigations. The in vitro experiments revealed that all tested compounds were significantly potent for α‐glucosidase inhibition, with the lead compound 3a displaying approximately 80 times higher activity than acarbose. To delve deeper, in silico induced fit docking, pharmacokinetics, and molecular dynamics studies were conducted. Significantly, compound 3a exhibited a docking score of −7.87 kcal/mol, surpassing acarbose, which had a docking score of −6.59 kcal/mol. The in silico ADMET indicated that most of the synthesized compounds have properties conducive to drug development. Molecular dynamics analysis demonstrated that, when the ligand 3a was coupled with the target 3TOP, Cα‐RMSD backbone RMSD values below 2.4 Å and “Lig_fit_Prot” values below 2.7 Å were observed. QSAR analysis demonstrates that the “fOC8A” descriptor positively correlates with α‐glucosidase inhibition activity, while “lipoplus_AbSA” positively contributes and “notringC_notringO_8B” negatively contributes to this activity.

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Synthesis, biological evaluation, and molecular modelling of substituted thiazolyl thiourea derivatives: A new class of prolyl oligopeptidase inhibitors

Naseem,

Oneto,

Ullah

et al. 2024

International Journal of Biological Macromolecules

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Synthesis, in vitro biological analysis and molecular docking studies of new thiadiazole-based thiourea derivatives as dual inhibitors of a-amylase and a-glucosidase

Cited by 6 publications

References 35 publications

Developing Correlation Between In Silico Molecular Modeling and In Vitro α‐Amylase, Anti‐Cancer and SARS‐COV‐2 Studies of Bis‐Indole Derived Triazine‐Based Thiazolidinone Hybrid Derivatives

Developing Correlation Between In Silico Molecular Modeling and In Vitro α‐Amylase, Anti‐Cancer and SARS‐COV‐2 Studies of Bis‐Indole Derived Triazine‐Based Thiazolidinone Hybrid Derivatives

Carbonylbis(hydrazine‐1‐carbothioamide) derivatives as a new class of α‐glucosidase inhibitors and their mechanistic insights via molecular docking and dynamic simulations

Synthesis, biological evaluation, and molecular modelling of substituted thiazolyl thiourea derivatives: A new class of prolyl oligopeptidase inhibitors

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