Chemical Behavior and Bioactive Properties of Spinorphin Conjugated to 5,5′-Dimethyl- and 5,5′-Diphenylhydantoin Analogs
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry of Spinorphine Derivatives
2.2. Analytical Characteristics
2.3. Determination of Hydrolytic Stability
2.4. Results for Anticonvulsant Activity
2.5. Antioxidant Activity Test
3. Materials and Methods
3.1. Synthesis of Peptide Analogues
General Procedure for the Peptide Synthesis of Compounds (Dm-S, Dm-S5, Dm-S6, Ph-S, Ph-S5, and Ph-S6)
3.2. Physicochemical Characterization
3.2.1. Determination of Partition Coefficient
3.2.2. Voltamperometric Analysis
3.2.3. Hydrolytic Activity Testing
3.2.4. pK and pI Determination
3.2.5. Spectral Characterizations
3.3. Study of Bioactive Properties
3.3.1. Pharmacology: In Vivo Experiments
- Animals:
- Drugs and dosage
- Seizure tests
- Maximal electroshock Test (MES test).
- Rota-rod test
- Statistical analysis
3.3.2. Microbiological Analyses: Antibacterial Activity, Antifungal, and Antioxidant Test
- Antibacterial Activity Test
- Antifungal Activity
- Antioxidant Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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№ | Peptide | a [α]54620 (o) | Molecular Formula | b tR, min | c [MH] + Calculated | c [MH] + Observed | LogP | pKa1 | pKa2 | pI1; pI2 |
---|---|---|---|---|---|---|---|---|---|---|
S | H-Leu-Val-Val-Tyr-Pro-Trp-Thr-NH2 | −74 | C45H65N9O9 | 20.04 | 876.0525 | 876.4970 | 0.421 | 3.15 | 6.78 | 4.91; 8.31 |
Dm-S | Dm-Leu-Val-Val-Tyr-Pro-Trp-Thr-NH2 | −70 | C52H73N11O12 | 26.88 | 1044.2025 | 1044.5501 | 1.16 | 3.18 | 7.16 | 5.07; 8.35 |
Dm-S5 | Dm-Leu-Val-Val-Tyr-Ac5c-Trp-Thr-NH2 | −20 | C53H75N11O12 | 33.76 | 1058.2291 | 1058.5654 | 1.08 | 3.19 | - | 4.91; 8.30 |
Dm-S6 | Dm-Leu-Val-Val-Tyr-Ac6c-Trp-Thr-NH2 | −32 | C54H77N11O12 | 36.63 | 1072.2557 | 1072.5814 | 0.934 | 3.31 | 7.23 | 5.04; 8.31 |
Ph-S | Ph-Leu-Val-Val-Tyr-Pro-Trp-Thr-NH2 | −68 | C62H77N11O12 | 38.64 | 1168.3413 | 1168.5799 | 1.01 | 3.20 | - | 5.06 |
Ph-S5 | Ph-Leu-Val-Val-Tyr-Ac5c-Trp-Thr-NH2 | −72 | C63H79N11O12 | 45.72 | 1182.3679 | 1182.5957 | 1.24 | 3.22 | - | 5.09 |
Ph-S6 | Ph-Leu-Val-Val-Tyr-Ac6c-Trp-Thr-NH2 | −20 | C64H81N11O12 | 45.00 | 1196.3944 | 1196.6118 | 1.35 | 3.21 | 6.84 | 5.06; 8.06 |
Group | Dose µg/10 µL | No. of Animals Protected/No. of Animals Tested | % Protection |
---|---|---|---|
control | 0 | 0/8 | 0% |
S | 0.62 | 3/6 | 50% |
1.25 | 3/6 | 50% | |
2.5 | 4/6 | 67% * | |
Dm-S | 0.62 | 2/6 | 33% |
1.25 | 2/6 | 33% | |
2.5 | 2/6 | 33% | |
Dm-S5 | 0.62 | 2/5 | 40% |
1.25 | 2/5 | 40% | |
2.5 | 3/6 | 50% | |
Dm-S6 | 0.62 | 1/6 | 17% |
1.25 | 3/6 | 50% | |
2.5 | 3/6 | 50% |
Group | Dose µg/10 µL | No. of Animals Protected/No. of Animals Tested | % Protection |
---|---|---|---|
control | 0 | 0/8 | 0% |
Ph-S | 0.62 | 4/6 | 33% |
1.25 | 4/6 | 67% * | |
2.5 | 2/6 | 67% * | |
Ph-S5 | 0.62 | 1/6 | 17% |
1.25 | 3/6 | 50% | |
2.5 | 3/6 | 50% | |
Ph-S6 | 0.62 | 1/6 | 17% |
1.25 | 3/6 | 50% | |
2.5 | 4/6 | 67% * |
Group | Dose µg/10 µL | No. of Animals Protected/No. of Animals Tested | % Protection | % Mortality |
---|---|---|---|---|
control | 0 | 0/8 | 0% | 30% |
S | 0.62 | 2/6 | 40% | 0% |
1.25 | 2/6 | 40% | 30% | |
2.5 | 3/6 | 50% | 50% | |
Dm-S | 0.62 | 0/6 | 0% | 83% |
1.25 | 1/6 | 17% | 33% | |
2.5 | 2/6 | 33% | 50% | |
Dm-S5 | 0.62 | 0/6 | 0% | 33% |
1.25 | 1/6 | 17% | 33% | |
2.5 | 2/6 | 33% | 33% | |
Dm-S6 | 0.62 | 1/6 | 17% | 33% |
1.25 | 2/6 | 33% | 50% | |
2.5 | 4/6 | 67% * | 0% |
Group | Dose µg/10 µL | No. of Animals Protected/No. of Animals Tested | % Protection | % Mortality |
---|---|---|---|---|
control | 0 | 0/8 | 0% | 30% |
Ph-S | 0.62 | 2/6 | 33% | 0% |
1.25 | 3/6 | 50% | 50% | |
2.5 | 3/6 | 50% | 17% | |
Ph-S5 | 0.62 | 2/6 | 33% | 50% |
1.25 | 3/6 | 50% | 33% | |
2.5 | 4/6 | 67% * | 17% | |
Ph-S6 | 0.62 | 2/6 | 40% | 60% |
1.25 | 3/6 | 50% | 67% | |
2.5 | 4/6 | 67% * | 17% |
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Georgieva, S.; Todorov, P.; Tchekalarova, J.; Subaer, S.; Peneva, P.; Chakarov, K.; Hartati, H.; Faika, S. Chemical Behavior and Bioactive Properties of Spinorphin Conjugated to 5,5′-Dimethyl- and 5,5′-Diphenylhydantoin Analogs. Pharmaceuticals 2024, 17, 770. https://doi.org/10.3390/ph17060770
Georgieva S, Todorov P, Tchekalarova J, Subaer S, Peneva P, Chakarov K, Hartati H, Faika S. Chemical Behavior and Bioactive Properties of Spinorphin Conjugated to 5,5′-Dimethyl- and 5,5′-Diphenylhydantoin Analogs. Pharmaceuticals. 2024; 17(6):770. https://doi.org/10.3390/ph17060770
Chicago/Turabian StyleGeorgieva, Stela, Petar Todorov, Jana Tchekalarova, Subaer Subaer, Petia Peneva, Kalin Chakarov, Hartati Hartati, and Sitti Faika. 2024. "Chemical Behavior and Bioactive Properties of Spinorphin Conjugated to 5,5′-Dimethyl- and 5,5′-Diphenylhydantoin Analogs" Pharmaceuticals 17, no. 6: 770. https://doi.org/10.3390/ph17060770
APA StyleGeorgieva, S., Todorov, P., Tchekalarova, J., Subaer, S., Peneva, P., Chakarov, K., Hartati, H., & Faika, S. (2024). Chemical Behavior and Bioactive Properties of Spinorphin Conjugated to 5,5′-Dimethyl- and 5,5′-Diphenylhydantoin Analogs. Pharmaceuticals, 17(6), 770. https://doi.org/10.3390/ph17060770