Nimesulide linked acyl thioureas potent carbonic anhydrase I, II and α-glucosidase inhibitors: Design, synthesis and molecular docking studies

Ahmed, Atteeque; Shafique, Imran; Saeed, Aamer; Shabir, Ghulam; Saleem, Arslan; Taslimi, Parham; Tok, Tuğba Taşkın; Kırıcı, Mahinur; Üç, Eda Mehtap; Hashmi, Muhammad Zaffar

doi:10.1016/j.ejmcr.2022.100082

Cited by 14 publications

(4 citation statements)

References 48 publications

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“… 24 Acyl thiourea derivatives, on the other hand, exhibit a diverse range of medicinal characteristics, including antifungal, 25 anti-tuberculosis, antimicrobial, 26 antioxidant, antibacterial, 27 anticancer, 28 anti-phenoloxidase and rodenticidal activities. 29 Many of these applications rely on the structural and conformational features of 1-acyl thiourea. The formation of appropriate hydrogen bonds with specific receptors in particular is a critical factor that plays a role in many fields, including analytical applications of 1-acyl thiourea as a chemo sensor for selective and sensitive naked-eye recognition of anions, as well as chemical biology and drug design.…”

Section: Introductionmentioning

confidence: 99%

Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies

Saeed,

Ahmed,

Haider

et al. 2024

RSC Adv.

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Section: Introductionmentioning

confidence: 99%

Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies

Saeed,

Ahmed,

Haider

et al. 2024

RSC Adv.

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“…Several thiourea derivatives inhibit transmembrane‐anchored carbonic anhydrases (Moeker et al., 2012), DNA gyrase and topoisomerase IV (Hashem et al., 2020), acetylcholinesterase and butyrylcholinesterase (Naz et al., 2020), and α‐glucosidase (Ullah et al., 2023). Some linked acyl thioureas are potent carbonic anhydrase I, II, and α‐glucosidase inhibitors (Ahmed et al., 2022; Hussain et al., 2022), antimicrobial agents (Hafsa et al., 2023), and antidiabetics (Khan et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

Sulfonyl thiourea derivatives from 2‐aminodiarylpyrimidines: In vitro and in silico evaluation as potential carbonic anhydrase I, II, IX, and XII inhibitors

Thanh,

Giang,

Hai

et al. 2024

Chem Biol Drug Des

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A series of synthesized sulfonyl thiourea derivatives (7a–o) of substituted 2‐amino‐4,6‐diarylpyrimidines (4a–o) exhibited the remarkable inhibitory activity against some the human carbonic anhydrases (hCAs), including hCA I, II, IX, and XII isoforms. The inhibitory efficacy of synthesized sulfonyl thiourea derivatives were experimentally validated by in vitro enzymatic assays. 7a (KI = 46.14 nM), 7j (KI = 48.92 nM), and 7m (KI = 62.59 nM) (for isoform hCA I); 7f (KI = 42.72 nM), 7i (KI = 40.98 nM), and 7j (KI = 33.40 nM) (for isoform hCA II); 7j (KI = 228.5 nM), 7m (KI = 195.4 nM), and 7n (KI = 210.1 nM) (for isoform hCA IX); 7l (KI = 116.9 nM), 7m (KI = 118.8 nM), and 7n (KI = 147.2 nM) (for isoform hCA XII) in comparison with KI values of 452.1, 327.3, 437.2, and 338.9 nM, respectively, of the standard drug AAZ. These compounds also had significantly more potent inhibitory action against cytosolic isoform hCA I and tumor‐associated isoforms hCA IX and hCA XII. Furthermore, the potential inhibitory compounds were subjected to in silico screening for molecular docking and molecular dynamics simulations. The results of in vitro and in silico studies revealed that compounds 7a, 7j, and 7m were the most promising derivatives in this series due to their significant effects on studied hCA I, II, IX, and XII isoforms, respectively. The results showed that the sulfonyl thiourea moiety was accommodated deeply in the active site and interacted with the zinc ion in the receptors.

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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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Nimesulide linked acyl thioureas potent carbonic anhydrase I, II and α-glucosidase inhibitors: Design, synthesis and molecular docking studies

Cited by 14 publications

References 48 publications

Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies

Novel pyrazoline linked acyl thiourea pharmacophores as antimicrobial, urease, amylase and α-glucosidase inhibitors: design, synthesis, SAR and molecular docking studies

Sulfonyl thiourea derivatives from 2‐aminodiarylpyrimidines: In vitro and in silico evaluation as potential carbonic anhydrase I, II, IX, and XII inhibitors

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

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