Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin-Thiazole Derivatives as α-Glucosidase Inhibitors

Xie, Zhenzhen; Wang, Guangcheng; Wang, Jing; Chen, Ming; Peng, Yaping; Li, Luyao; Deng, Bing; Chen, Shan; Li, Wenbiao

doi:10.3390/molecules22040659

Cited by 47 publications

(15 citation statements)

References 36 publications

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“…The present results in the molecular docking study of the ursane-type triterpenes show similarities with previous studies on α-glucosidase targeting [37,[43][44][45]. According to Dubey et al, a docking study of rutin was visualized by Discovery Studio, in which rutin demonstrated an inhibition constant of 67.62 µm and binding energy of −7.01 kcal/mol with α-glucosidase (PDB ID: 3A4A) by non-covalent interaction [37].…”

Section: Discussionsupporting

confidence: 87%

“…The stereochemical aspects of the model were inspected by checking the Ramachandran plot (see Supplementary Materials); it can be considered a liable model for further docking studies. This homology modeling was used to investigate the interactions of compounds with the active site of α-glucosidase [43,44,47]. The crystal structure of human intestinal α-glucosidase in a complex with acarbose inhibitor (PDB ID: 3TOP) was retrieved from the PDB.…”

Section: Molecular Docking Study For Anti-α-glucosidase Inhibitionmentioning

confidence: 99%

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Inhibition of α-Glucosidase, Acetylcholinesterase, and Nitric Oxide Production by Phytochemicals Isolated from Millettia speciosa—In Vitro and Molecular Docking Studies

Tuan

Thi

et al. 2022

Plants

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The phytochemical constituents from the roots of Millettia speciosa were investigated by chromatographic isolation, and their chemical structures were characterized using the MS and NMR spectroscopic methods. A total of 10 compounds, including six triterpenoids, two flavonoids, and two phenolic compounds, were identified from the roots of M. speciosa. Out of the isolated compounds, eight showed inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC50 values ranging from 43.9 to 449.5 µg/mL. Ursane-type triterpenes significantly suppressed NO production compared to the remaining compounds. In addition, these compounds also exhibited remarkable inhibitory effects on α-glucosidase. Among the tested compounds, 4, 5, and 10 exhibited excellent α-glucosidase inhibition, with IC50 values ranging from 1.1 to 2.2 µg/mL. Almost all of the test compounds showed little or no acetylcholinesterase inhibition, except for 5, which showed moderate anti-acetylcholinesterase activity in vitro. The molecular docking study of α-glucosidase inhibition by 3–5 and 10 was conducted to observe the interactions of these molecules with the enzyme. Compounds 4, 5, and 10 exhibited a better binding affinity toward the targeted receptor and the H-bond interactions located at the entrance of the enzyme active site pocket in comparison to those of 3 and the positive control acarbose. Our findings evidence the pharmacological potential of this species and suggest that the phytochemicals derived from the roots of M. speciosa may be promising lead molecules for further studies on the development of anti-inflammatory and anti-diabetes drugs.

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Section: Discussionsupporting

confidence: 87%

Section: Molecular Docking Study For Anti-α-glucosidase Inhibitionmentioning

confidence: 99%

Inhibition of α-Glucosidase, Acetylcholinesterase, and Nitric Oxide Production by Phytochemicals Isolated from Millettia speciosa—In Vitro and Molecular Docking Studies

Tuan

Thi

et al. 2022

Plants

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“…1 ) induced better α-glucosidase inhibitory activity than other derivatives 16 . Also, the same trend was observed by Xie et al, so the 2-fluorobenzyl moiety of isatin-thiazole scaffold disclosed better potency in comparison to different derivatives 42 . These results are in line with the current study.…”

Section: Resultssupporting

confidence: 79%

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Iraji

Shareghi-Brojeni

Mojtabavi

et al. 2022

Sci Rep

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In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.

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“…The Indolin-2-one ring of 69p established a CH-π interaction with Phe-157, whereas the 4-hydroxylphenyl group displayed a CH-π interaction with Phe-158 and Tyr-71 as well as forming arene anion interactions with Asp-68 and Asp-349. In addition, arene–anion interactions were observed between Arg-439, Arg-443, and 69p , whereas compound 69p established H-bond interactions with Thr-215, Asp-68, and Glu-276, which were important interactions for α-glucosidase inhibition [ 90 ]. In another study endeavoring to find a potent α-glucosidase inhibitor, a group in 2018 also designed chromone–isatin hybrids ( 70a – p , Figure 9 ), which were found to display excellent a-glucosidase inhibitory potential with IC 50 values in the range of 3.18 ± 0.12–16.59 ± 0.17 μM.…”

Section: Development Of Isatin Derivatives As Promising Therapeutic A...mentioning

confidence: 99%

Therapeutic Outcomes of Isatin and Its Derivatives against Multiple Diseases: Recent Developments in Drug Discovery

Cheke¹,

Patil²,

Firke

et al. 2022

Pharmaceuticals

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Isatin (1H indole 2, 3-dione) is a heterocyclic, endogenous lead molecule recognized in humans and different plants. The isatin nucleus and its derivatives are owed the attention of researchers due to their diverse pharmacological activities such as anticancer, anti-TB, antifungal, antimicrobial, antioxidant, anti-inflammatory, anticonvulsant, anti-HIV, and so on. Many research chemists take advantage of the gentle structure of isatins, such as NH at position 1 and carbonyl functions at positions 2 and 3, for designing biologically active analogues via different approaches. Literature surveys based on reported preclinical, clinical, and patented details confirm the multitarget profile of isatin analogues and thus their importance in the field of medicinal chemistry as a potent chemotherapeutic agent. This review represents the recent development of isatin analogues possessing potential pharmacological action in the years 2016–2020. The structure–activity relationship is also discussed to provide a pharmacophoric pattern that may contribute in the future to the design and synthesis of potent and less toxic therapeutics.

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Synthesis, Biological Evaluation, and Molecular Docking Studies of Novel Isatin-Thiazole Derivatives as α-Glucosidase Inhibitors

Cited by 47 publications

References 36 publications

Inhibition of α-Glucosidase, Acetylcholinesterase, and Nitric Oxide Production by Phytochemicals Isolated from Millettia speciosa—In Vitro and Molecular Docking Studies

Inhibition of α-Glucosidase, Acetylcholinesterase, and Nitric Oxide Production by Phytochemicals Isolated from Millettia speciosa—In Vitro and Molecular Docking Studies

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Therapeutic Outcomes of Isatin and Its Derivatives against Multiple Diseases: Recent Developments in Drug Discovery

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