Interactions of Some Chemotherapeutic Agents as Epirubicin, Gemcitabine and Paclitaxel in Multicomponent Systems Based on Orange Essential Oil
Abstract
:1. Introduction
2. Results and Discussion
2.1. Experimental Results
2.1.1. Spectrophotometric Study
2.1.2. Electrochemical Study
2.1.3. Kinetic Approach
2.2. Theoretical Study
2.2.1. Analysis of HOMO-LUMO Frontier Orbitals
2.2.2. Global Chemical Reactivity
2.2.3. Limonene-Chemotherapeutic Agent Interactions
2.3. Decomposition Mechanism of Drugs
2.3.1. Epirubicin Decomposition Mechanism
2.3.2. Gemcitabine Decomposition Mechanism
2.3.3. Paclitaxel Decomposition Mechanism
3. Materials and Methods
3.1. Materials
3.2. Preparation of Work Environments
3.3. Investigation Methods
3.3.1. UV-Vis Spectrophotometry
3.3.2. Electrochemical Measurements
3.4. Theoretical Study
3.4.1. Molecular Modelling
3.4.2. Docking Protocol
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Molecular Structures of Drugs | UV-Vis Spectra of Compounds in Studied Media | λmax/nm |
---|---|---|
Limonene (LIM); C10H16; M = 136.23 g mol−1 | | LIM 274 nm 252 nm |
Epirubicin (EPR); C27H29NO11 × HCl; M = 543.174 g mol−1 | | EPR 500 nm |
Gemcitabine (GCT); C9H11F2N3O4; M = 263.2 g mol−1 | | GCT 278 nm |
Paclitaxel (PTX); C47H51NO14; M = 853.331 g mol−1 | | PTX 230 nm |
CYT/Environment | First-Order Reaction Kinetics | Zero-Order Reaction Kinetics | ||||
---|---|---|---|---|---|---|
Ao/Experimental | Ao/Computed from Ao= Ae−kt | R2 | Ao/Experimental | Ao/Computed from Ao = A − kt | R2 | |
EPR_HCl | 2.01 | 2.07 | 0.996 | - | - | - |
EPR_SE | 2.54 | 2.38 | 0.988 | - | - | - |
EPR_ESO | 2.86 | 2.35 | 0.967 | - | - | - |
GCT_HCl | - | - | - | 2.62 | 2.64 | 0.997 |
GCT_SE | - | - | - | 2.6 | 2.55 | 0.994 |
GCT_ESO | 4.12 | 4.16 | 0.994 | 4.16 | 3.93 | 0.960 |
PTX_HCl | - | - | - | 2.21 | 2.16 | 0.998 |
PTX_SE | - | - | - | 2.34 | 2.28 | 0.994 |
PTX_ESO | - | - | - | 2.11 | 2.12 | 0.995 |
CYT/Environment | First Order Reaction Kinetics | Zero Order Reaction Kinetics | |||
---|---|---|---|---|---|
ln(Ao/A) = kt | A = Aoe−kt | t1/2 = (ln2)/k | A = Ao − kt | t1/2 = Ao/2k | |
k (min−1) | t1/2 (min) | k (uA min−1) | t1/2 (min) | ||
EPR_HCl | 0.062 | 0.0621 | 11.2 | - | - |
EPR_SE | 0.015 | 0.0152 | 46.2 | - | - |
EPR_ESO | 0.011 | 0.0109 | 63.0 | - | - |
GCT_HCl | - | - | - | 0.3114 | 4.2 |
GCT_SE | - | - | - | 0.2065 | 6.2 |
GCT_ESO | 0.081 | 0.081 | 8.6 | - | - |
PTX_HCl | - | - | - | 0.069 | 15.7 |
PTX_SE | - | - | - | 0.0317 | 35.9 |
PTX_ESO | - | - | - | 0.0412 | 25.8 |
Descriptors | Chemical Compound | |||
---|---|---|---|---|
EPR | GCT | PTX | LIM | |
EHOMO | −9.049 | −9.673 | −8.863 | −9.181 |
ELUMO | −1.657 | −0.559 | −0.387 | 1.345 |
I/eV | 9.049 | 9.673 | 8.863 | 9.181 |
A/eV | 1.657 | 0.559 | 0.387 | −1.345 |
ΔE/eV | 7.392 | 9.114 | 8.476 | 10.256 |
χ/eV | 5.353 | 5.116 | 4.625 | 3.918 |
η/eV | 3.696 | 4.557 | 4.238 | 5.263 |
S/eV−1 | 0.271 | 0.219 | 0.236 | 0.19 |
ε/eV | −5.353 | −5.116 | −4.625 | −3.918 |
ω/eV | 3.87 | 2.87 | 2.52 | 1.45 |
Dipole moment/D | 1.77 | 6.598 | 3.67 | 0.904 |
Binding Energy (Kcal mol−1) | Chemotherapeutic Agent-Limonene | ||
---|---|---|---|
EPR-LIM | GCT-LIM | PTX-LIM | |
Final intermolecular energy | −3.58 | −1.86 | −3.93 |
Final total internal energy | −4.59 | −1.99 | −10.06 |
Torsion free energy | +3.28 | +1.49 | +5.07 |
Free binding energy of chemotherapeutic agent-limonene (ΔG) | −0.30 | −0.37 | +1.14 |
Drug | λmax/nm | A | C/g L−1 | C/mol L−1 | Volume of Drug Solution |
---|---|---|---|---|---|
Epirubicin | 500 | 2.01 | 0.14 | 2.57 × 10−4 | 70 |
Gemcitabine | 278 | 2.62 | 0.04 | 1.52 × 10−4 | 1 |
Paclitaxel | 230 | 2.21 | 0.01 | 1.17 × 10−5 | 1.7 |
Solution | Volume from Basic Drug Solution/mL | 5 × 10−2 mol L−1 HCl Solution/mL | DESSO/mL | Water/mL | Ethanol/mL |
---|---|---|---|---|---|
EPR_HCl | 70 | 50 | - | 880 | - |
EPR_SE | 70 | 50 | - | 480 | 400 |
EPR_ESO | 70 | 50 | 1 | 481 | 399 |
GCT_HCl | 1 | 50 | - | 880 | - |
GCT_SE | 1 | 50 | - | 480 | 400 |
GCT_ESO | 1 | 50 | 1 | 481 | 399 |
PTX_HCl | 1.7 | 50 | - | 880 | - |
PTX_SE | 1.7 | 50 | - | 480 | 400 |
PTX_ESO | 1.7 | 50 | 1 | 481 | 399 |
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Samide, A.; Tutunaru, B.; Varut, R.-M.; Oprea, B.; Iordache, S. Interactions of Some Chemotherapeutic Agents as Epirubicin, Gemcitabine and Paclitaxel in Multicomponent Systems Based on Orange Essential Oil. Pharmaceuticals 2021, 14, 619. https://doi.org/10.3390/ph14070619
Samide A, Tutunaru B, Varut R-M, Oprea B, Iordache S. Interactions of Some Chemotherapeutic Agents as Epirubicin, Gemcitabine and Paclitaxel in Multicomponent Systems Based on Orange Essential Oil. Pharmaceuticals. 2021; 14(7):619. https://doi.org/10.3390/ph14070619
Chicago/Turabian StyleSamide, Adriana, Bogdan Tutunaru, Renata-Maria Varut, Bogdan Oprea, and Simona Iordache. 2021. "Interactions of Some Chemotherapeutic Agents as Epirubicin, Gemcitabine and Paclitaxel in Multicomponent Systems Based on Orange Essential Oil" Pharmaceuticals 14, no. 7: 619. https://doi.org/10.3390/ph14070619