Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Synthesis
Comp. No. | R | Cryst. Solv. | Mp (°C) | Yield (%) | Molecular Formula (Mol. Wt.) |
---|---|---|---|---|---|
5a | C2H5 | EtOH | 150–152 | 77 | C17H29N3S (307.50) |
5b | COOC2H5 | EtOH | 121–123 | 68 | C18H29N3O2S (351.51) |
5c | C6H5 | EtOH | 174–176 | 91 | C21H29N3S (355.54) |
5d | 2-CH3OC6H4 | EtOH | 137–139 | 95 | C22H31N3OS (385.57) |
5e | C6H5CH2 | EtOH | 146–148 | 95 | C22H31N3S (369.57) |
6 | - | EtOH | 139–141 | 88 | C15H24N2OS (280.43) |
7 | - | EtOH | 175–177 | 74 | C15H24N2S (264.43) |
8a | H | EtOH | 145–147 | 78 | C16H26N2S (278.46) |
8b | C6H5 | EtOH | 137–139 | 90 | C22H30N2S (354.55) |
8c | COOC2H5 | EtOH | 166–168 | 78 | C19H30N2O2S (350.52) |
9 | - | EtOH | 147–149 | 88 | C20H26N2S (326.5) |
10a | H | DMF | 227–229 | 89 | C26H40N4S2 (472.75) |
10b | CH3 | DMF | 232–234 | 92 | C28H44N4S2 (500.81) |
14a | CH3 | EtOH | 200–202 | 38 | C19H29N5S2 (391.6) |
14b | C6H5 | DMF | >300 | 44 | C24H31N5S2 (453.67) |
15a | 2-OH | EtOH | 196–198 | 65 | C24H32N4O2S (440.6) |
15b | 3,4-Cl2 | EtOH/CHCl3 | 237–237 | 61 | C24H30Cl2N4OS (493.49) |
15c | 2,6-Cl2 | EtOH | 199–201 | 54 | C24H30Cl2N4OS (493.49) |
15d | 3,4-(OCH3)2 | EtOH | 154–156 | 48 | C26H36N4O3S (484.65) |
15e | 3,4,5-(OCH3)3 | EtOH | 128–130 | 43 | C27H38N4O4S (514.68) |
15f | 2-OH-5-OCH3 | EtOH/CHCl3 | 170–172 | 44 | C25H34N4O3S (470.63) |
15g | 3-OC2H5-4-OH | EtOH/CHCl3 | 194–196 | 58 | C26H36N4O3S (484.65) |
2.2. In Vitro Antimicrobial Activity
Comp. No. | Clog P | Diameter of Growth Inhibition Zone (mm) a | |||||
---|---|---|---|---|---|---|---|
SA | BS | ML | EC | PA | CA | ||
5a | 4.32 | - | - | - | - | - | - |
5b | 4.32 | - | - | - | - | - | - |
5c | 4.77 | 20 (8) b | 24 (2) b | 16 | 15 | 14 | - |
5d | 4.79 | 19 (4) b | 22 (4) b | 17 | 12 | - | - |
5e | 5.52 | 15 | 19 (8) b | 12 | 15 | 12 | - |
6 | 3.23 | 22 (2) b | 20 (1) b | 19 (4) b | 15 | 12 | - |
7 | 4.06 | 18 (8) b | 20 (2) b | 18 (4) b | 15 | 13 | - |
8a | 4.62 | 12 | 14 | 12 | - | - | - |
8b | 6.03 | 16 | 16 | 14 | - | - | - |
8c | 4.01 | 12 | 13 | - | - | - | - |
9 | 5.48 | - | - | - | - | - | - |
10a | 6.86 | 25 (32) b | 28 (16) b | 20 (32) b | 18 | 16 | - |
10b | 7.90 | 26 (32) b | 24 (8) b | 23 (32) b | 19 (64) b | 12 | - |
14a | 3.40 | - | - | - | - | - | - |
14b | 5.29 | - | - | - | - | - | - |
15a | 5.07 | 18 (16) b | 22 (2) b | 15 | 12 | - | - |
15b | 5.77 | 12 | 12 | - | - | - | - |
15c | 4.70 | 14 | 17 | 12 | - | - | - |
15d | 4.41 | - | - | - | - | - | - |
15e | 4.03 | - | - | - | - | - | - |
15f | 5.14 | 22 (8) b | 27 (1) b | 19 (8) b | 13 | 11 | 11 |
15g | 4.79 | 19 (8) b | 25 (2) b | 18 (8) b | 12 | 12 | 13 |
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% |
5c (10 mg/kg) | 291.6 ± 15.23 | 189.0 ± 22.16 * | 35.19% (92.48) |
5c (20 mg/kg) | 319.6 ± 7.85 | 207.0 ± 13. 84 * | 35.23% (46.30) |
6 (10 mg/kg) | 283.8 ± 11.16 | 263.8 ± 16.66 | 7.05% (18.52) |
6 (20 mg/kg) | 296.6 ± 12.92 | 196.0 ± 9.67 * | 33.92% (44.58) |
8b (10 mg/kg) | 264.2 ± 5.49 | 257.4 ± 9.45 | 2.57% (6.75) |
8b (20 mg/kg) | 303.3 ± 16.35 | 291.2 ± 8.18 | 4.05% (5.32) |
9 (10 mg/kg) | 282.8 ± 13.90 | 275.8 ± 15.52 | 2.48% (6.52) |
9 (20 mg/kg) | 276.2 ± 14.17 | 264.6 ± 7.35 | 4.20% (5.52) |
14a (10 mg/kg) | 274.8 ± 14.59 | 277.4 ± 7.19 | 0.95% (2.50) |
14a (20 mg/kg) | 286.4 ± 24.56 | 271.4 ± 21.85 | 5.24% (6.89) |
15b (10 mg/kg) | 282.0 ± 14.21 | 287.8 ± 13.37 | −2.06% |
15b (20 mg/kg) | 293.2 ± 15.66 | 286.8 ± 17.16 | 2.18% (2.87) |
2.4. Oral Acute Toxicity Testing of Compound 5c
3. Experimental Section
3.1. General
3.2. Synthesis of N-(1-Adamantyl)-4-substituted piperazine-1-carbothioamides 5a–e, N-(1-Adamantyl)morpholine-4-carbothioamide 6, N-(1-Adamantyl)pyrrolidine-1-carbothioamide 7, N-(1-Adamantyl)-4-substituted piperidine-1-carbothioamides 8a–c and N-(1-Adamantyl)-1,2,3,4-tetrahydroisoquinoline-2-carbothioamide 9
3.3. Synthesis of N,N'-Bis(1-adamantyl)piperazine-1,4-dicarbothioamide 10a and trans-N,N'-Bis(1-adamantyl)-2,5-dimethylpiperazine-1,4-dicarbothioamide 10b
3.4. Synthesis of 1-(1-Adamantylthiocarbamoyl)piperidine-4-carbohydrazide 11 and 4-(1-Adamanty)-3-thiosemicarbazide 12
3.5. Synthesis of N-(1-Adamantyl)piperidine-4-(5-mercapto-4-phenyl-1,2,4-triazol-3-yl)-1-carbothioamide 14a,b
3.6. Synthesis of 1-[(1-Adamantyl)thiocarbamoyl)]-N'-(arylidene)piperidine-4-carbohydrazides 15a–g
3.7. Determination of the in Vitro Antimicrobial Activity (Agar Disc-Diffusion Method)
3.8. Determination of the Minimal Inhibitory Concentration (MIC)
3.9. Determination of the in Vivo Hypoglycemic Activity
3.10. Determination of the Oral Acute Toxicity of Compound 5c
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Al-Abdullah, E.S.; Al-Tuwaijri, H.M.; Hassan, H.M.; Al-Alshaikh, M.A.; Habib, E.E.; El-Emam, A.A. Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives. Molecules 2015, 20, 8125-8143. https://doi.org/10.3390/molecules20058125
Al-Abdullah ES, Al-Tuwaijri HM, Hassan HM, Al-Alshaikh MA, Habib EE, El-Emam AA. Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives. Molecules. 2015; 20(5):8125-8143. https://doi.org/10.3390/molecules20058125
Chicago/Turabian StyleAl-Abdullah, Ebtehal S., Hanaa M. Al-Tuwaijri, Hanan M. Hassan, Monirah A. Al-Alshaikh, Elsayed E. Habib, and Ali A. El-Emam. 2015. "Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives" Molecules 20, no. 5: 8125-8143. https://doi.org/10.3390/molecules20058125