Antimicrobial and Hypoglycemic Activities of Novel N-Mannich Bases Derived from 5-(1-Adamantyl)-4-substituted-1,2,4-triazoline-3-thiones
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
Comp. No. | R | R' | Cryst. Solv. | m.p. (°C) | Yield (%) | Molecular Formula (Mol. Wt.) |
---|---|---|---|---|---|---|
6a | C2H5 | C2H5 | EtOH/H2O | 158–160 | 77 | C21H35N5S (389.6) |
6b | C2H5 | COOC2H5 | EtOH/H2O | 153–155 | 72 | C22H35N5O2S (433.61) |
6c | C2H5 | C6H5 | EtOH | 139–141 | 88 | C25H35N5S (437.64) |
6d | C2H5 | 2-CH3OC6H4 | EtOH | 204–206 | 92 | C26H37N5OS (467.67) |
6e | C2H5 | C6H5CH2 | EtOH | 168–170 | 81 | C26H37N5S (451.67) |
6f | C2H5 | 2-Pyridyl | EtOH/H2O | 144–146 | 92 | C24H34N6S (438.63) |
6g | CH2=CHCH2 | C2H5 | EtOH/H2O | 109–111 | 66 | C22H35N5S (401.61) |
6h | CH2=CHCH2 | COOC2H5 | EtOH/H2O | 114–116 | 60 | C23H35N5O2S (445.62) |
6i | CH2=CHCH2 | C6H5 | EtOH | 161–163 | 69 | C26H35N5S (449.65) |
6j | CH2=CHCH2 | 2-CH3OC6H4 | EtOH | 208–210 | 74 | C27H37N5OS (479.68) |
6k | CH2=CHCH2 | C6H5CH2 | EtOH/H2O | 109–111 | 59 | C27H37N5S (463.68) |
6l | CH2=CHCH2 | 2-Pyridyl | EtOH/H2O | 133–135 | 66 | C25H34N6S (450.64) |
2.2. In Vitro Antimicrobial Activity
Comp. No. | Clog p | Diameter of Growth Inhibition Zone (mm) a | |||||
---|---|---|---|---|---|---|---|
SA | BS | ML | EC | PA | CA | ||
6a | 3.96 | – | – | – | – | – | – |
6b | 5.51 | – | – | – | – | – | – |
6c | 5.67 | – | – | – | – | – | – |
6d | 5.69 | 15 | 17 | 11 | – | – | – |
6e | 6.59 | 21 (8) b | 20 (4) b | 17 | 14 | – | – |
6f | 4.72 | 15 | 18 (8) b | 11 | – | – | – |
6g | 4.21 | 11 | 13 | – | – | – | – |
6h | 5.76 | – | 12 | – | – | – | – |
6i | 5.92 | 14 | 16 | 12 | – | – | – |
6j | 5.82 | 19 (8) b | 18 (16) b | 18 (16) b | – | – | – |
6k | 6.84 | 28 (0.5) b | 30 (0.5) b | 19 (8) b | 18 (16) b | 12 | – |
6l | 4.97 | 17 | 19 (8) b | 10 | – | – | – |
Gentamicin | 26 (2) b | 25 (2) b | 18 (2) b | 20 (0.5) b | 19 (1) b | NT | |
Ampicillin | 23 (2) b | 21 (0.5) b | 19 (2) b | 17 (2) b | 16 (2) b | NT | |
Clotrimazole | NT | NT | NT | NT | NT | 21 (2) b |
2.3. In Vivo Hypoglycemic Activity
Treatment | Results | ||
---|---|---|---|
C0 (mg/dL) a | C24 (mg/dL) a | % Glucose Reduction b | |
Group 1 c | 302.6 ± 11.64 | 287.2 ± 16.85 | 5.09% |
Group 2 d | 295.4 ± 17.52 | 183.0 ± 13.38 * | 38.05% |
6a (10 mg/kg) | 289.0 ± 18.05 | 204.4 ± 7.37 * | 29.27% (76.93%) |
6a (20 mg/kg) | 290.4 ± 10.60 | 188.0 ± 8.6 * | 35.26% (46.34%) |
6c (10 mg/kg) | 285.8 ± 14.31 | 241.6 ± 19.2 | 15.47% (40.66%) |
6c (20 mg/kg) | 297.6 ± 18.57 | 245.4 ± 11.54 | 17.54% (23.05%) |
6f (10 mg/kg) | 289.0 ± 14.35 | 197.8 ± 6.13 * | 31.56% (82.94%) |
6f (20 mg/kg) | 292.6 ± 10.33 | 189.0 ± 7.42 * | 35.41% (46.53%) |
6g (10 mg/kg) | 291.0 ± 5.58 | 190.6 ± 9.05 * | 34.50% (90.67%) |
6g (20 mg/kg) | 283.4 ± 10.45 | 184.0 ± 15.28 * | 35.07% (46.09%) |
6j (10 mg/kg) | 278.4 ± 15.07 | 228.4 ± 11.41 | 17.96% (47.20%) |
6j (20 mg/kg) | 297.4 ± 17.94 | 203.4 ± 15.28 * | 31.61% (41.54%) |
6l (10 mg/kg) | 290.4 ± 18.37 | 199.0 ± 18.75 * | 31.47% (82.71%) |
6l (20 mg/kg) | 295.4 ± 12.58 | 200.0 ± 18.78 * | 32.30% (42.45%) |
2.4. Oral Acute Toxicity Testing
Comp. No. | LD50 * | LD50 (95% Confidence Limit) |
---|---|---|
6a | 892 ± 38.70 | 892 (844–1089) |
6f | 787 ± 41.05 | 787 (721–923) |
6g | 833 ± 23.80 | 833 (765–891) |
6l | 741 ± 22.50 | 741 (624–806) |
3. Experimental Section
3.1. General
3.2. General Procedure for the Preparation of 5-(1-Adamantyl)-4-ethyl or allyl-2-(4-substituted piperazine-1-ylmethyl)-1,2,4-triazoline-3-thiones 6a–l
3.3. Determination of the in Vitro Antimicrobial Activity (Agar Disc-Diffusion Method)
3.4. Determination of the Minimal Inhibitory Concentration (MIC)
3.5. Determination of the in Vivo Hypoglycemic Activity
3.6. Determination of the Oral Acute Toxicity of Compounds 6a, 6f, 6g and 6l
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Al-Abdullah, E.S.; Al-Tuwaijri, H.M.; Hassan, H.M.; Haiba, M.E.; Habib, E.E.; El-Emam, A.A. Antimicrobial and Hypoglycemic Activities of Novel N-Mannich Bases Derived from 5-(1-Adamantyl)-4-substituted-1,2,4-triazoline-3-thiones. Int. J. Mol. Sci. 2014, 15, 22995-23010. https://doi.org/10.3390/ijms151222995
Al-Abdullah ES, Al-Tuwaijri HM, Hassan HM, Haiba ME, Habib EE, El-Emam AA. Antimicrobial and Hypoglycemic Activities of Novel N-Mannich Bases Derived from 5-(1-Adamantyl)-4-substituted-1,2,4-triazoline-3-thiones. International Journal of Molecular Sciences. 2014; 15(12):22995-23010. https://doi.org/10.3390/ijms151222995
Chicago/Turabian StyleAl-Abdullah, Ebtehal S., Hanaa M. Al-Tuwaijri, Hanan M. Hassan, Mogedda E. Haiba, Elsayed E. Habib, and Ali A. El-Emam. 2014. "Antimicrobial and Hypoglycemic Activities of Novel N-Mannich Bases Derived from 5-(1-Adamantyl)-4-substituted-1,2,4-triazoline-3-thiones" International Journal of Molecular Sciences 15, no. 12: 22995-23010. https://doi.org/10.3390/ijms151222995