Synthesis of Novel Triazinoindole-Based Thiourea Hybrid: A Study on α-Glucosidase Inhibitors and Their Molecular Docking

A new class of triazinoindole-bearing thiosemicarbazides (1–25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared to standard acarbose (an IC50 value of 38.60 ± 0.20 µM). Among the series, analogs 1 and 23 were found to be the most potent, with IC50 values of 1.30 ± 0.05 and 1.30 ± 0.01 µM, respectively. The structure–activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.

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Synthesis of novel Triazinoindole-Based-Thiourea Hybrid: α-Glucosidase Inhibitors and Their Molecular Docking Study

10.20944/preprints201909.0130.v1 ◽

2019 ◽

Author(s):

Muhammad Taha ◽

Foziah J. Alshamrani ◽

Fazal Rahim ◽

Shawkat Hayat ◽

Hayat Ullah ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Molecular Docking Study ◽

Glucosidase Inhibitors ◽

13C Nmr Analysis ◽

Ic50 Value ◽

Phenyl Rings ◽

Ic50 Values ◽

Inhibitory Potential ◽

Alpha Glucosidase

New class of triazinoindole bearing thiosemicarbazide (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogues exhibited excellent inhibitory potential having IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared with the standard acarbose having IC50 value 38.60 ± 0.20 µM. Among series the analogues 1 and 23 was found the most potent having IC50 values 1.30 ± 0.05 and 1.30 ± 0.01 µM respectively. Structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl rings. To confirm the binding interactions, molecular docking study was performed. Synthesized analogues were characterized through HREI-MS, 1H and 13C-NMR analysis.

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Synthesis of Diabetic II Inhibitors Based on 2-mercaptobenzimidazole and their Molecular Docking Study

10.20944/preprints201911.0375.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Muhammad Taha ◽

Fazal Rahim ◽

Shawkat Hayat ◽

Manikandan Selvaraj ◽

Rai Khalid Farooq ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Binding Mode ◽

Alpha Amylase ◽

Variable Degree ◽

Molecular Docking Study ◽

Standard Drug ◽

Ic50 Value ◽

Ic50 Values ◽

Inhibitory Potential

In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1-17) and evaluated for their α-amylase inhibitory potential. All compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. The remaining analogs showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR. Structure activity relationship (SAR) has been recognized for all newly synthesized analogs. Through molecular docking study, binding mode of active analogs with α-amylase enzyme was confirmed.

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Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study

Molecules ◽

10.3390/molecules24061002 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1002 ◽

Cited By ~ 3

Author(s):

Noor Almandil ◽

Muhammad Taha ◽

Rai Farooq ◽

Amani Alhibshi ◽

Mohamed Ibrahim ◽

...

Keyword(s):

Molecular Docking ◽

Thymidine Phosphorylase ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Substitution Pattern ◽

Structure Activity ◽

Ic50 Value ◽

Quinoxaline Derivatives ◽

Better Than

We have synthesized quinoxaline analogs (1–25), characterized by 1H-NMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent compound among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21 and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure-activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

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3-Benzyl(phenethyl)-2-thioxobenzo[g]quinazolines as a new class of potent α-glucosidase inhibitors: synthesis and molecular docking study

Future Medicinal Chemistry ◽

10.4155/fmc-2018-0141 ◽

2018 ◽

Vol 10 (16) ◽

pp. 1889-1905 ◽

Cited By ~ 11

Author(s):

Rashad Al-Salahi ◽

Rohaya Ahmad ◽

ElHassane Anouar ◽

Nor Izzati Iwana Nor Azman ◽

Mohamed Marzouk ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Molecular Docking Study ◽

New Class ◽

Glucosidase Inhibitors

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Thiazole Based Carbohydrazide Derivatives as α-Amylase Inhibitor and Their Molecular Docking Study

Heteroatom Chemistry ◽

10.1155/2019/7502347 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Muhammad Taha ◽

Maryam Irshad ◽

Syahrul Imran ◽

Fazal Rahim ◽

Manikandan Selvaraj ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Study ◽

Docking Studies ◽

Antidiabetic Agent ◽

Molecular Docking Study ◽

Binding Interaction ◽

Structure Activity ◽

Inhibitory Potential ◽

Amylase Inhibitors

In this study we are going to present thiazole based carbohydrazide in search of potent antidiabetic agent as α-amylase inhibitors. Thiazole based carbohydrazide derivatives 1-25 have been synthesized, characterized by 1HNMR, 13CNMR, and EI-MS, and evaluated for α-amylase inhibition. Except compound 11 all analogs showed α-amylase inhibitory activity with IC50 values from 1.709 ± 0.12 to 3.049 ± 0.25 μM against the standard acarbose (IC50 = 1.637 ± 0.153 μM). Compounds 1, 10, 14, and 20 exhibited outstanding inhibitory potential with IC50 value 1.763 ± 0.03, 1.747 ± 0.20, 1.709 ± 0.12, and 1.948 ± 0.23 μM, respectively, compared with the standard acarbose. Structure activity relationships have been established for the active compounds. To get an idea about the binding interaction of the compounds, molecular docking studies were done.

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Synthesis of Thymidine Phosphorylase Inhibitor Based on Quinoxaline Derivatives and Their Molecular Docking Study

10.20944/preprints201901.0086.v1 ◽

2019 ◽

Author(s):

Noor Barak Almandil ◽

Muhammad Taha ◽

Rai Khalid Farooq ◽

Amani Alhibshi ◽

Mohamed Ibrahim ◽

...

Keyword(s):

Molecular Docking ◽

Thymidine Phosphorylase ◽

Docking Study ◽

Docking Studies ◽

Molecular Docking Study ◽

Substitution Pattern ◽

Structure Activity ◽

Ic50 Value ◽

Quinoxaline Derivatives ◽

Better Than

We have synthesized quinoxaline analogs (1-25), characterized by 1HNMR and HREI-MS and evaluated for thymidine phosphorylase inhibition. Among the series, nineteen analogs showed better inhibition when compared with the standard inhibitor 7-Deazaxanthine (IC50 = 38.68 ± 4.42 µM). The most potent analog among the series is analog 25 with IC50 value 3.20 ± 0.10 µM. Sixteen analogs 1, 2, 3, 4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 18, 21and 24 showed outstanding inhibition which is many folds better than the standard 7-Deazaxanthine. Two analogs 8 and 9 showed moderate inhibition. A structure- activity relationship has been established mainly based upon the substitution pattern on the phenyl ring. The binding interactions of the active compounds were confirmed through molecular docking studies.

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Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

Scientific Reports ◽

10.1038/s41598-021-91473-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fariba Peytam ◽

Ghazaleh Takalloobanafshi ◽

Toktam Saadattalab ◽

Maryam Norouzbahari ◽

Zahra Emamgholipour ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Rat Small Intestine ◽

Molecular Docking Study ◽

Design Synthesis ◽

Mild Conditions ◽

Glucosidase Inhibitors ◽

Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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