Designing Click One-Pot Synthesis and Antidiabetic Studies of 1,2,3-Triazole Derivatives
Abstract
:1. Introduction
1.1. Target Selection
1.2. Dataset Collection
1.3. Lead Identification and Analogue Design
2. Results and Discussion
2.1. Virtual Screening for Antidiabetic Compounds
2.2. Drug-Likeness and ADMET Properties
2.3. Molecular Docking Analysis
2.4. In Vitro Antidiabetic Assay
3. Materials and Methods
3.1. Materials
3.2. Experimental Equipment
3.3. Docking Procedure
3.4. Synthesis of the Hits Identified
General Procedure for the Synthesis
3.5. In Vitro Analysis
3.5.1. α-Amylase Inhibition Assay
3.5.2. Alpha-Glucosidase Inhibition Assay
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Compound 1 KS-1, 15.90 ± 0.91 µM | Compound 2 KS-2 > 100 µM |
Compound 3 KS-03, 11.82 ± 0.82 | Compound 4 KS-04, 29.84 ± 3.47 |
Compound 5 KS-05, 2.06 ± 0.16 | Compound 6 KS-06, 8.31 ± 0.88 |
Compound 7 KS-07, 2.78 ± 0.22 | Compound 8 KS-08, 3.07 ± 0.56 |
Compound 9 KS-09, 6.13 ± 0.09 | Compound 10 KS-10, 7.06 ± 0.89 |
Compound 11 KS-11, 5.23 ± 0.53 | Compound 12 KS-12, 3.17 ± 0.61 |
Compound 13 KS-13, 17.61 ± 1.68 | Compound 14 KS-14, 15.62 ± 1.13 |
Compound 15 KS-15, 5.87 ± 0.76 | Compound 16 KS-16, 5.88 ± 0.32 |
Compound 17 KS-17, 98.63 ± 4.12 | Compound 18 KS-18, >100 |
Compound 19 KS-19, 26.11 ± 2.95 | Compound 20 KS-20, 32.33 ± 0.82 |
Compound 21 KS-21, 33.16 ± 2.51 | Compound 22 KS-22, 42.60 ± 0.09 |
Compound 23 KS-23, 12.78 ± 0.01 | Compound 24 KS-24, 12.13 ± 1.84 |
Compound 25 KS-25, 28.7 | Compound 26 KS-26, >100 |
Compound 27, KS-27, 37.4 | Compound 28, KS-28, 61.1 |
Compound 29 KS-29, 27.4 | Compound 30 KS-30, >100 |
Compound 31 KS-31, >100 | Compound 32 KS-32, 41.0 |
Compound 33 KS-33, 29.4 | Compound 34 KS-34, 45.9 |
Compound 35 KS-35, 48.4 | Compound 36 KS-36, 33.6 |
Compound 37 KS-37, 28.2 | Compound 38, KS-38 |
Compound 39 KS-39 | Compound 40 KS-40 |
Compound 41 KS-41 | Compound 42 KS-42 |
Compound 43 KS-43 | Compound 44 KS-44 |
Compound 45 KS-45 | Compound 46 KS-46 |
Compound 47 KS-47 | Compound 48 KS-48 |
Compound 49 KS-49 | Compound 50 KS-50 |
Compound 51 KS-51 | Compound 52 KS-52 |
Compound 53 KS-53 | Compound 54 KS-54 |
Compound 55 KS-55 | Standard 1 Sitagliptin |
Standard 2 Alogliptin | Standard 3 Metformin |
Sr. No | Molecular Wt. g/mol | Log P | Rotatable Bonds | Acceptors | Donors | Surface Area (g/cm2) |
---|---|---|---|---|---|---|
01 | 321.4 | 3.1 | 6 | 5 | 01 | 140.4 |
02 | 231.3 | 2.5 | 4 | 5 | 0 | 99.2 |
03 | 249.3 | 2.9 | 4 | 3 | 0 | 112.1 |
04 | 235.3 | 3.7 | 3 | 3 | 0 | 105.9 |
Sr. No | Absorption mg/L | Distribution mg/L | Metabolism mg/L | Excretion mg/L | Toxicity Oral/Hepatotoxicity |
---|---|---|---|---|---|
01 | 98.726 | 0.128 | Yes | 0.394 | No/No |
02 | 94.696 | 0.271 | Yes | 0.327 | 0.23/No |
03 | 97.12 | 0.088 | Yes | 0.272 | No/No |
04 | 94.539 | 0.191 | Yes | 0.28 | 0.8/No |
Sr. No | Compounds | Hydrogen Bonding | Arene–pi Interactions | Binding Energy (S) | |
---|---|---|---|---|---|
01 | K-1 | 2.74, 2.86 1.13, 2.64 2.59 | Tyr18, Ser39, Tyr24, Arg37, Asn136 | -- | −0.6467 |
02 | S-2 | 2.48, 1.8, 2.52 | Lys36, Ser39 | Yes | −4.0720 |
03 | K-2 | 2.47, 2.02 | Lys33, Trp141 | -- | −3.0564 |
04 | H-4 | 2.32, 1.15 | Gyl151, Ser150 | yes | −2.5427 |
Dose µg/mL | %Age Inhibition at Different Concentration | |||||||
---|---|---|---|---|---|---|---|---|
800 | 400 | 200 | 100 | 50 | 25 | 12.5 | 6.25 | |
K-1 | 87.012 | 81.11 | 74.89 | 64.24 | 55.81 | 42.21 | 37.23 | 23.11 |
S-2 | 84.22 | 78.56 | 71.59 | 59.1 | 52.22 | 44.81 | 32.22 | 21.47 |
K-2 | 81.89 | 73.45 | 58.23 | 48.56 | 39.76 | 29.34 | 20.42 | 12.78 |
H-4 | 83.12 | 76.11 | 64.72 | 53.12 | 45.12 | 39.12 | 25.1 | 16.89 |
%Age Inhibition at Different Concentrations | ||||||||
---|---|---|---|---|---|---|---|---|
Dose µg/mL | 800 | 400 | 200 | 100 | 50 | 25 | 12.5 | 6.25 |
K-1 | 99.17 | 97.01 | 95.55 | 91.11 | 88.96 | 83.11 | 72.37 | 68.04 |
S-2 | ±96.22 | ±95.01 | 93.81 | 90.24 | 86.02 | 72.41 | 69.23 | 65.10 |
K-2 | 87.19 | 83.12 | 71.03 | 65.10 | 57.8 | 51.69 | 44.32 | 31.09 |
H-4 | 89.12 | 81.01 | 75.00 | 67.11 | 55.21 | 49.11 | 40.81 | 41.09 |
Samples | Reactants | Product | Yield | |||||
---|---|---|---|---|---|---|---|---|
A | B | C | R1 | R2 | R3 | |||
K-1 | ethyl 2-(1-benzyl-4-phenyl-1 H-1,2,3-triazol-5-yl)acetate | 79% | ||||||
S-2 | 1,5-dibenzyl-4-phenyl-1H-56%1,2,3-triazole | 71% | ||||||
K-2 | NaN3 | H | ethyl 2-(4-phenyl-1H-1,2,3-triazol-5-yl)acetate | 56% | ||||
H-4 | NaN3 | H | 5-benzyl-4-phenyl-1H-1,2,3-triazole | 67% |
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Shafique, K.; Farrukh, A.; Mahmood Ali, T.; Qasim, S.; Jafri, L.; Abd-Rabboh, H.S.M.; AL-Anazy, M.m.; Kalsoom, S. Designing Click One-Pot Synthesis and Antidiabetic Studies of 1,2,3-Triazole Derivatives. Molecules 2023, 28, 3104. https://doi.org/10.3390/molecules28073104
Shafique K, Farrukh A, Mahmood Ali T, Qasim S, Jafri L, Abd-Rabboh HSM, AL-Anazy Mm, Kalsoom S. Designing Click One-Pot Synthesis and Antidiabetic Studies of 1,2,3-Triazole Derivatives. Molecules. 2023; 28(7):3104. https://doi.org/10.3390/molecules28073104
Chicago/Turabian StyleShafique, Kainat, Aftab Farrukh, Tariq Mahmood Ali, Sumera Qasim, Laila Jafri, Hisham S. M. Abd-Rabboh, Murefah mana AL-Anazy, and Saima Kalsoom. 2023. "Designing Click One-Pot Synthesis and Antidiabetic Studies of 1,2,3-Triazole Derivatives" Molecules 28, no. 7: 3104. https://doi.org/10.3390/molecules28073104