Figure 1
Figure 2
Figure 3
ADME and toxicity predictions of compounds MK1 and MK2
| Properties | MK1 | MK2 |
|---|---|---|
| Molecular weight (Da) | 211.26 | 225.29 |
| Number of rotatable bonds | 3 | 3 |
| Number of hydrogen bond donors | 0 | 0 |
| Number of hydrogen bond acceptors | 2 | 2 |
| TPSA (Å2) | 21.59 | 21.59 |
| Lipophilicity: XLOGP3 (log Po/w) | 2.79 | 3.56 |
| Lipophilicity: consensus (log Po/w) | 3.15 | 3.58 |
| Gastrointestinal absorption | High | High |
| Water solubility (log S) (calculated with the ESOL model) | −3.26 | −3.80 |
| BBB permeation | Yes | Yes |
| Lipinski’s rules (violations) | 0 | 0 |
| Clinical toxicity | No | No |
| Predicted median lethal dose (LD50) (mg/kg) | 500 | 500 |
| Max. tolerated dose in humans (Log mg/kg/day) | 0.799 | 0.761 |
| hERG I inhibitor | No | No |
| hERG II inhibitor | No | No |
| Carcinogenicity | No | No |
| Cardiotoxicity | No | No |
| Hepatotoxicity | No | No |
| Nephrotoxicity | No | No |
| Nutritional toxicity | No | No |
| Respiratory toxicity | No | No |
| Skin sensitization | Yes | Yes |
Anti-glucosidase potentials of the synthesized compounds in terms of their IC50 values
| Sample | Glucosidase IC50 (μg/mL) |
|---|---|
| MK1 | 281.23 |
| MK2 | 204.69 |
| Acarbose | 46.81 |
Animal’s grouping and dosing details
| S. no. | Group | No. of rats | Treatment | Dose (mg) | Route of drug administration |
|---|---|---|---|---|---|
| 1 | Control | 04 | Normal saline | 10 | PO |
| 2 | Diabetic | 04 | Normal saline | 10 | PO |
| 3 | Diabetic | 04 | MK-1 | 25 | PO |
| 4 | Diabetic | 04 | MK-1 | 50 | PO |
| 5 | Diabetic | 04 | MK-2 | 25 | PO |
| 6 | Diabetic | 04 | MK-2 | 50 | PO |
| 7 | Diabetic | 04 | Standard drug (glibenclamide) | 5 | PO |
Effects of various drug agents at different concentrations on the HBA1c in STZ diabetic rats
| Days | NC | DC | MK1 (25 mg) | MK1 (50 mg) | MK2 (25 mg) | MK2 (50 mg) | STD | |
|---|---|---|---|---|---|---|---|---|
| HBA1c | Mean | 4.54 | 14.76 | 9.67 | 7.92 | 7.98 | 7.51 | 5.07 |
| SEM | 0.22 | 1.44 | 0.45 | 0.41 | 0.53 | 0.42 | 0.18 |
Antioxidant potentials of the synthesized compounds in terms of their IC50 values
| Sample | DPPH IC50 (μg/mL) |
|---|---|
| MK1 | 131.67 |
| MK2 | 112.04 |
| Tocopherol | 15.92 |
Blood glucose levels (mg/dL) of rats treated with various drug agents at different concentrations
| Days | NC | DC | MK1 (25 mg) | MK1 (50 mg) | MK2 (25 mg) | MK2 (50 mg) | STD | |
|---|---|---|---|---|---|---|---|---|
| Day 1 | Mean | 103.32 | 459.15 | 463.67 | 459.98 | 471.05 | 464.33 | 460.48 |
| SEM | 2.18 | 7.19 | 7.32 | 6.61 | 5.84 | 7.00 | 6.31 | |
| Day 7 | Mean | 98.62 | 477.13 | 406.37 | 365.83 | 379.15 | 359.95 | 328.42 |
| SEM | 2.57 | 6.20 | 4.24 | 5.23 | 5.33 | 4.80 | 4.41 | |
| Day 14 | Mean | 102.62 | 469.05 | 323.77 | 291.47 | 298.17 | 294.93 | 265.25 |
| SEM | 2.36 | 6.26 | 5.32 | 4.06 | 4.04 | 3.53 | 3.47 | |
| Day 21 | Mean | 103.83 | 461.57 | 236.65 | 201.18 | 202.70 | 177.53 | 156.12 |
| SEM | 3.60 | 6.46 | 3.65 | 3.16 | 3.65 | 2.13 | 2.99 | |
| Day 28 | Mean | 100.55 | 454.63 | 175.47 | 146.82 | 139.02 | 121.23 | 111.67 |
| SEM | 2.09 | 6.34 | 4.24 | 3.47 | 4.76 | 4.20 | 2.82 |
Effect of various drug agents at different concentrations on body weight of STZ-induced diabetic rats
| Days | NC | DC | MK1 (25 mg) | MK1 (50 mg) | MK2 (25 mg) | MK2 (50 mg) | STD | |
|---|---|---|---|---|---|---|---|---|
| Day 1 | Mean | 179.72 | 180.65 | 175.43 | 176.42 | 177.98 | 175.42 | 176.08 |
| SEM | 2.56 | 2.02 | 3.78 | 2.13 | 2.94 | 1.92 | 2.91 | |
| Day 28 | Mean | 174.72 | 149.50 | 165.15 | 164.98 | 167.32 | 168.13 | 170.53 |
| SEM | 2.62 | 2.88 | 3.37 | 2.41 | 3.61 | 2.69 | 2.16 |
Physical parameters of the synthesized compounds
| Comp | Structure | Mol. formula | Appearance | Molecular weight. | Yield% | Solubility | m.p. (°C) | r.f. | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| MK1 |
| C14H13NO | Yellowish white solid | 211.26 | 768.1 | Chloroform, methanol | 64–68 | 0.57 | [51,52] |
| MK2 |
| C14H12ClNO | White solid | 245.71 | 74.2 | Chloroform, methanol | 119–121 | 0.66 | [53] |
Effects of various drug agents at different concentrations on the lipid profile of STZ-induced diabetic rats
| Biomarker | NC | DC | MK1 (25 mg) | MK1 (50 mg) | MK2 (25 mg) | MK2 (50 mg) | STD | |
|---|---|---|---|---|---|---|---|---|
| HDL | Mean | 38.40 | 118.33 | 85.62 | 76.53 | 66.39 | 61.12 | 47.29 |
| SEM | 1.77 | 5.87 | 4.79 | 4.20 | 2.94 | 3.69 | 4.00 | |
| LDL | Mean | 66.22 | 37.23 | 44.04 | 49.33 | 47.58 | 48.89 | 58.19 |
| SEM | 3.95 | 2.25 | 2.22 | 2.51 | 2.35 | 2.92 | 3.78 | |
| TG | Mean | 105.30 | 215.92 | 145.15 | 129.01 | 130.05 | 118.15 | 109.73 |
| SEM | 3.31 | 7.80 | 3.67 | 5.75 | 5.23 | 4.12 | 4.07 | |
| CH | Mean | 59.25 | 205.72 | 102.46 | 91.94 | 87.21 | 74.42 | 64.28 |
| SEM | 2.64 | 8.23 | 2.75 | 3.27 | 3.06 | 2.52 | 4.64 | |
| ALP | Mean | 115.45 | 237.03 | 146.65 | 132.78 | 145.92 | 134.49 | 123.82 |
| SEM | 5.11 | 11.15 | 4.79 | 3.79 | 3.37 | 2.49 | 5.53 |
Binding scores, RMSD values, receptor interactions, distances, and energies of methoxy-substituted Schiff bases (MK1 and MK2)
| Ligand | Docking score (kcal/mol) | RMSD | Receptor interaction | Distance (Å) | E (kcal/mol) |
|---|---|---|---|---|---|
| MK1 | −5.22 | 1.29 | TRP329/H–pi | 3.80 | −1.3 |
| ALA234/pi–H | 4.22 | −0.5 | |||
| MK2 | −5.73 | 2.04 | ARG670/pi–cation | 3.54 | −0.8 |
| GLU792/pi–H | 4.09 | −0.9 |