Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Synthesis
2.2. Crystallographic Studies
2.3. In Vitro Antimicrobial Activity
2.4. In Vivo Hypoglycemic Activity
3. Materials and Methods
3.1. General
3.2. Synthesis of 4-Arylmethyl (Z)-N′-(Adamantan-1-yl)-Morpholine-4-Carbothioimidates 7a–e and 4-Arylmethyl (Z)-N′-(Adamantan-1-yl)-4-Phenylpiperazine-1-Carbothioimidates 8a–e
3.3. Crystal Growth and Single Crystal X-ray Study
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of all compounds are available from the correspondent author. |
Comp. No. | R | Cryst. Solv. | M.p. (°C) | Yield (%) | Mol. Formula (Mol. Wt.) |
---|---|---|---|---|---|
7a | H | EtOH/H2O | 108–110 | 91 | C22H30N2OS (370.55) |
7b | 4-Cl | EtOH | 92–94 | 76 | C22H29ClN2OS (405.0) |
7c | 4-Br | EtOH | 98–100 | 85 | C22H29BrN2OS (449.45) |
7d | 4-NO2 | EtOH | 118–120 | 95 | C22H29N3O3S (415.55) |
7e | 3,5-(CF3)2 | EtOH/H2O | 106–108 | 72 | C24H28F6N2OS (506.55) |
8a | H | EtOH/H2O | 137–139 | 88 | C28H35N3S (445.66) |
8b | 4-Cl | EtOH | 153–155 | 90 | C28H34ClN3S (480.11) |
8c | 4-Br | EtOH | 140–142 | 92 | C28H34BrN3S (524.56) |
8d | 4-NO2 | EtOH | 145–147 | 96 | C28H34N4O2S (490.66) |
8e | 3,5-(CF3)2 | EtOH/H2O | 113–115 | 75 | C30H33F6N3S (581.66) |
Data | Compound 7d | Compound 8d |
---|---|---|
Formula | C22H29N3O3S | C28H34N4O2S |
Formula weight | 415.55 | 490.66 |
Temperature (K) | 293 | 293 |
Wavelength (Å) | 0.71073 | 0.71073 |
Crystal system | Monoclinic | Orthorhombi |
Space group | P21/c | P212121 |
a, b, c (Å) | 6.9204 (5), 29.775 (3), 10.2725 (10) | 6.9426 (9), 9.6472 (12), 39.086 (5) |
V (Å3) | 2116.7 (3) | 2617.8 (6) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
μ (mm−1) | 0.18 | 0.16 |
No. of reflections | 11033 | 25091 |
No. of unique reflections/obs. reflections | 3718/2253 | 4609/1447 |
No. of parameters | 262 | 318 |
No. of restraints | 0 | 0 |
Δρmax, Δρmin (e Å−3) | 0.28, −0.21 | 0.44, −0.40 |
Tmin, Tmax | 0.939, 0.989 | 0.924, 0.957 |
Rint | 0.073 | 0.526 |
Crystal size (mm) | 0.35 × 0.11 × 0.06 | 0.85 × 0.21 × 0.05 |
R[F2 > 2σ(F2)], wR(F2), S | 0.052, 0.192, 0.65 | 0.128, 0.296, 1.02 |
CCDC number | 1525183 | 1523432 |
Comp. No. | Clog P | Diameter of Growth Inhibition Zone (mm) a | |||||
---|---|---|---|---|---|---|---|
SA | BS | ML | EC | PA | CA | ||
7a | 5.584 | 22 (2) b | 21 (4) b | 20 (4) b | 18 (16) b | 14 (64) b | - |
7b | 6.297 | 24 (4) b | 28 (0.5) b | 22 (4) b | 22 (20) b | 15 (32) | 11 (>128) b |
7c | 6.447 | 22 (4) b | 18 (16) b | 14 (64) b | 13 (128) b | 12 (128) b | - |
7d | 5.327 | 31 (0.5) b | 32 (0.25) b | 28 (0.5) b | 22 (1) b | 18 (4) b | 14 (32) b |
7e | 7.350 | 33 (0.25) b | 34 (0.25) b | 28 (1) b | 24 (2) b | 20 (4) b | - |
8a | 7.130 | 18 (8) b | 18 (8) b | 14 (128) b | 12 (>128) b | 10 (>128) b | 10 (>128) b |
8b | 7.843 | 21 (8) b | 24 (2) b | 16 (32) b | 16 (64) b | 12 (>128) b | 13 (64) b |
8c | 7.993 | 17 (32) b | 19 (8) b | 14 (64) b | 11 (>128) b | 10 (>128) b | 12 (128) b |
8d | 6.873 | 24 (1) b | 28 (1) b | 20 (2) b | 18 (2) b | 14 (4) b | 16 (16) b |
8e | 8.896 | 28 (1) b | 31 (0.5) b | 22 (2) b | 19 (4) b | 18 (8) b | 14 (64) b |
Gentamicin sulfate | 27 (1) b | 26 (2) b | 20 (2) b | 22 (0.5) b | 21 (0.5) b | NT | |
Ampicillin trihydrate | 22 (2) b | 23 (1) b | 20 (2) b | 16 (8) b | 16 (8) b | NT | |
Clotrimazole | NT | NT | NT | NT | NT | 21 (4) b |
Treatment | Results | ||
---|---|---|---|
C0 (mg/dL) a | C24 (mg/dL) a | % Glucose Reduction b | |
Group 1 c | 302.8 ± 11.64 | 290.2 ± 18.22 | 4.16% |
Group 1 d | 299.2 ± 16.50 | 171.6 ± 12.32 * | 42.65% |
7a (10 mg/kg) | 304.8 ± 13.26 | 212.4 ± 12.16 * | 30.31% (71.08) |
7a (20 mg/kg) | 300.6 ± 11.65 | 134.6 ± 9.75 * | 55.22% (64.74) |
7b (10 mg/kg) | 288.9 ± 12.15 | 245.2 ± 19.25 * | 15.13% (35.47) |
7b (20 mg/kg) | 294.8 ± 9.08 | 201.5 ± 9.60 * | 31.65% (37.13) |
7c (10 mg/kg) | 284.8 ± 19.55 | 281.2 ± 7.19 | 1.26% (2.69) |
7c (20 mg/kg) | 290.2 ± 21.64 | 286.8 ± 19.02 | 2.75% (1.37) |
7d (10 mg/kg) | 278.1 ± 16.24 | 282.2 ± 27.20 | −1.47% |
7d (20 mg/kg) | 302.6 ± 22.25 | 299.8 ± 18.80 | 0.93% (1.08) |
7e (10 mg/kg) | 306.2 ± 15.20 | 198.7 ± 19.10 * | 35.12 (82.32) |
7e (20 mg/kg) | Toxic | ||
8a (10 mg/kg) | 294.6 ± 11.30 | 200.2 ± 9.88 * | 32.04% (75.13) |
8a (20 mg/kg) | 290.6 ± 8.60 | 108.4 ± 11.05 * | 62.70% (73.50) |
8b (10 mg/kg) | 301.4 ± 9.06 | 199.8 ± 10.01 * | 33.71% (79.04) |
8b (20 mg/kg) | 296.0 ± 11.02 | 144.6 ± 10.01 * | 51.15% (59.96) |
8c (10 mg/kg) | 320.5 ± 22.05 | 277.6 ± 16.20 | 13.39% (31.38) |
8c (20 mg/kg) | 313.5 ± 18.60 | 269.9 ± 20.12 | 13.91% (16.30) |
8d (10 mg/kg) | 295.0 ± 22.45 | 289.2 ± 25.28 | 1.97% (4.61) |
8d (20 mg/kg) | 304.5 ± 27.50 | 309.0 ± 25.95 | −1.48 |
8e (10 mg/kg) | 286.6 ± 13.22 | 178.2 ± 16.04 * | 37.82% (88.68) |
8e (20 mg/kg) | Toxic |
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Al-Wahaibi, L.H.; Hassan, H.M.; Abo-Kamar, A.M.; Ghabbour, H.A.; El-Emam, A.A. Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities. Molecules 2017, 22, 710. https://doi.org/10.3390/molecules22050710
Al-Wahaibi LH, Hassan HM, Abo-Kamar AM, Ghabbour HA, El-Emam AA. Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities. Molecules. 2017; 22(5):710. https://doi.org/10.3390/molecules22050710
Chicago/Turabian StyleAl-Wahaibi, Lamya H., Hanan M. Hassan, Amal M. Abo-Kamar, Hazem A. Ghabbour, and Ali A. El-Emam. 2017. "Adamantane-Isothiourea Hybrid Derivatives: Synthesis, Characterization, In Vitro Antimicrobial, and In Vivo Hypoglycemic Activities" Molecules 22, no. 5: 710. https://doi.org/10.3390/molecules22050710