Synthesis, In Vitro α-Glucosidase Inhibitory Activity and Molecular Docking Studies of Novel Benzothiazole-Triazole Derivatives

Gong, Zipeng; Peng, Yaping; Qiu, Jie; Cao, Anbai; Wang, Guangcheng; Peng, Zhiyuan

doi:10.3390/molecules22091555

Cited by 53 publications

(18 citation statements)

References 28 publications

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“…αGIs covers a good range of inhibitory activities. αGI 1 - αGI 16 , αGI 17 - αGI 33 , and αGI 34 - αGI 38 , are reported by Wang et al 2017, Taha et al 2008, and Alhassan et al 2018, respectively [ 42 , 43 , 44 , 45 ]. Based on the diversity of structure and the activity, the data was segregated into training and test sets of 32 and 6 compounds, respectively.…”

Section: Methodsmentioning

confidence: 81%

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Rational Design of Novel Inhibitors of α-Glucosidase: An Application of Quantitative Structure Activity Relationship and Structure-Based Virtual Screening

Halim

Jabeen²,

Khan

et al. 2021

Pharmaceuticals

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α-Glucosidase is considered a prime drug target for Diabetes Mellitus and its inhibitors are used to delay carbohydrate digestion for the treatment of diabetes mellitus. With the aim to design α-glucosidase inhibitors with novel chemical scaffolds, three folds ligand and structure based virtual screening was applied. Initially linear quantitative structure activity relationship (QSAR) model was developed by a molecular operating environment (MOE) using a training set of thirty-two known inhibitors, which showed good correlation coefficient (r2 = 0.88), low root mean square error (RMSE = 0.23), and cross-validated correlation coefficient r2 (q2 = 0.71 and RMSE = 0.31). The model was validated by predicting the biological activities of the test set which depicted r2 value of 0.82, indicating the robustness of the model. For virtual screening, compounds were retrieved from zinc is not commercial (ZINC) database and screened by molecular docking. The best docked compounds were chosen to assess their pharmacokinetic behavior. Later, the α-glucosidase inhibitory potential of the selected compounds was predicted by their mode of binding interactions. The predicted pharmacokinetic profile, docking scores and protein-ligand interactions revealed that eight compounds preferentially target the catalytic site of α-glucosidase thus exhibit potential α-glucosidase inhibition in silico. The α-glucosidase inhibitory activities of those Hits were predicted by QSAR model, which reflect good inhibitory activities of these compounds. These results serve as a guidelines for the rational drug design and development of potential novel anti-diabetic agents.

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Section: Methodsmentioning

confidence: 81%

“…A set of thirty-eight structurally diverse compounds ( αGIs ) with α-glucosidase inhibitory activities was retrieved from literature [ 42 , 43 , 44 , 45 ]. αGIs covers a good range of inhibitory activities.…”

Section: Methodsmentioning

confidence: 99%

Rational Design of Novel Inhibitors of α-Glucosidase: An Application of Quantitative Structure Activity Relationship and Structure-Based Virtual Screening

Halim

Jabeen²,

Khan

et al. 2021

Pharmaceuticals

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“…2 Triazoles are well-known pharmacological agents 3 due to a range of bioactivities including anticancer, 4 antimicrobial, 5−7 antidiabetic, 3−5,8−10 and antiobesity 10 ones. Different chromanochalcones bearing 1,2,3-triazole, 4 fluorinated 1,2,4-triazoles, 5 carbohydrate conjugated 1,2,3-triazoles, 8 and benzothiazoles bearing 1,2,3-triazole 9 were found to be active antidiabetic agents. α−Glucosidase (EC 3.2.1.20) is a glucosidase that works on 1,4-alpha bonds.…”

Section: Introductionmentioning

confidence: 99%

“…Commercially available α -glucosidase inhibitors such as acarbose, miglitol, and voglibose are widely used to treat patients with type II diabetes. [3][4][5][8][9][10]14 Some series of sulfonamides were previously synthesized by our group and found to possess inhibition potential against the α -glucosidase enzyme. 15−17 These compounds previously synthesized by our group and a literature review 3−5,8−10 of triazoles prompted us to synthesize some series of compounds bearing these active functionalities.…”

Section: Introductionmentioning

confidence: 99%

S -substituted derivatives of 1,2,4-triazol-3-thiol as new drug candidates for type II diabetes

et al. 2018

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The therapeutic applications of 1,2,4-triazoles motivated us to synthesize some new derivatives. Two series of S-substituted derivatives (8a-8j, 12a-12i) of 5-{ 1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl }-4-phenyl-4 H-1,2,4-triazol-3-thiol (6) have been synthesized and evaluated for their biological potential. Using 4-chlorobenzene sulfonyl chloride (1) and ethyl piperidine-3-carboxylate (2), ethyl 1-[(4-chlorophenyl)sulfonyl]piperidine-3-carboxylate (3) was synthesized and converted into 3,4,5-trisubstituted 1,2,4-triazole (6) through formation of the corresponding carbohydrazide (4) and hydrazinecarbothioamide (5). Compound 6 was transformed into 8a-8j by alkyl halides (7a-7j) and into 12a-12i by N-aralkyl/aryl-2-bromoacetamides (11a-11i) in an aprotic solvent. The electrophiles, 11a-11i, were synthesized by gearing up N-substituted aralkyl/aryl amines (10a-10i) with 2-bromoacetyl bromide (9) under dynamic pH control by aqueous sodium carbonate. Structures were elucidated through the spectral techniques of IR, EIMS, 1 H NMR, and 13 C NMR. Most of the synthesized derivatives were found to be potent inhibitors of α-glucosidase enzyme and even better than acarbose. Acarbose is a reference standard and is a commercially available α-glucosidase inhibitor to treat patients with type II diabetes. The low hemolytic activity also emphasized the potential of the synthesized compounds as new drug candidates.

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“…From the literatures, the benzothiazole and its derivatives used as virus inhibitors for (1-HIV), and protein activities inhibitors [3]. They contain two un homogenized atoms of (N, S), in which they give anti-inflammable activities [4], anti-tumors [5], anti-convulsant [6], anti-microbial [7], anti-malaria [8], anti-infection bacterial [9], anti-fungi [10], tuber clauses, anti-parasitic worms [11], and anti-diabetes [12]. The benzothiazole derivatives used as painkiller and reduce the muscle spasms and it interact with nerve transfer of glutamate in biochemical and electro-physiological experiments [13].…”

Section: -Introductionmentioning

confidence: 99%

Synthesis, Characterization and Biological Activity Evaluation of Some New Azo Derivatives from 2- Amino Benzothiazole and Their Derivatives

Ahmed¹,

Jebur²,

Hamzah³

2018

KUJSS

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Synthesis, In Vitro α-Glucosidase Inhibitory Activity and Molecular Docking Studies of Novel Benzothiazole-Triazole Derivatives

Cited by 53 publications

References 28 publications

Rational Design of Novel Inhibitors of α-Glucosidase: An Application of Quantitative Structure Activity Relationship and Structure-Based Virtual Screening

Rational Design of Novel Inhibitors of α-Glucosidase: An Application of Quantitative Structure Activity Relationship and Structure-Based Virtual Screening

S -substituted derivatives of 1,2,4-triazol-3-thiol as new drug candidates for type II diabetes

Synthesis, Characterization and Biological Activity Evaluation of Some New Azo Derivatives from 2- Amino Benzothiazole and Their Derivatives

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