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EVALUATION OF THE INTERACTION OF THREE TYPES OF ANTRACICLINES AND NEUROTRASMISORS USING QUANTIC CHEMICAL SIMULATION

Lillhian Arely Flores-Gonzáleza, Karina García-Aguilara,b, Iliana Herrera-Cantúa, Erick Pedraza-Gressa, Manuel Aparicio-Razoa,d, Oscar Sánchez-Paradac, Emmanuel Vázquez-Lópeza, Juan Jesús García-Mara and Manuel González-Péreza
aUniversidad Popular Autónoma del Estado de Puebla A.C. (UPAEP). Centro, Interdisciplinario de Posgrados (CIP). Posgrado en Ciencias de la Ingeniería Biomédica
bInstituto Tecnológico Superior de Coatzacoalcos (Académica de Ingeniería Bioquímica),
cEscuela de Medicina Universidad Popular Autónoma del Estado de Puebla (UPAEP),
dBenemérita Universidad Autónoma de Puebla, Facultad de Ciencias de la Electrónica

Actas del Congreso Nacional de Tecnología Aplicada a Ciencias de la Salud Vol. 2, 2019

RESUMEN

En este trabajo analizamos tres tipos de antraciclinas (ACys). El análisis consiste en observar cómo estos ACys interactúan con los neurotransmisores (NT). Estos medicamentos se usan en el tratamiento de diferentes tipos de cáncer en pacientes humanos. El programa Hyperchem se utilizó para realizar la simulación y los cálculos de variables cuánticas. Como resultado, los investigadores observamos que ACys tiene una alta probabilidad de interacción con NT. Esta interacción tiene diferentes efectos posibles dependiendo del compuesto que se analiza. Llegamos a la conclusión de que la parte del sistema nervioso central (SNC) que controla el estado de ánimo del paciente se ve afectada.

Palabra clave. Antraciclinas, neurotransmisores, Hyperchem, análisis cuántico

ABSTRACT

In this work we analyze three types of anthracyclines (ACys). The analysis consists of observing how these ACys interact with the neurotransmitters (NT). These drugs are used in the treatment of different types of cancer in human patients. The Hyperchem program was used to perform the simulation and calculations of quantum variables. As a result, we researchers observed that ACys have a high probability of interaction with NT. This interaction has different possible effects depending on the compound being analyzed. We conclude that the part of the central nervous system (CNS) that controls the mood of the patient is affected.

Keyword. Anthracyclines, Neurotransmitters, Hyperchem, Quantum Analysis

1. INTRODUCTION

Clinical use of the three ACys

Daunorubicin is a chemotherapeutic drug of the ACy family that is used to treat certain types of cancer. Some specific types of leukemia, such as acute myeloid leukemia and acute lymphoid leukemia [4].

Epirubicin is a medication that belongs to the ACy family and is used as chemotherapy to treat cancer. It causes fewer side effects due to its rapid elimination. It is primarily used in the treatment of breast cancer, ovarian cancer, stomach cancer, lung cancer and lymphomas [5-8].

Doxorubicin is a drug that belongs to the ACy family and is used as chemotherapy to treat cancer. Doxorubicin is commonly used in the treatment of some leukemia and Hodgkin's lymphoma, as well as cancer of the bladder, breast, stomach, lung, ovaries, thyroid, multiple myeloma and others [9-11].

Currently, there are no known studies that predict the effects of ACys on NT or AA. On the other hand, ACys attack DNA synthesis and replication, but very little is known about the active site of the attack to break the chain [12-13].

In the other hands, NTs are chemicals created by the body that transmit information signals from a neuron through contact points called synapses. The knowledge about neurotransmitters is fundamental to understand the human being. It is linked to the nervous system and the adaptation of the mind to each process [14-16].

Therefore, the article focuses on the quantum analysis of three basic types of ACys used for different types of cancer and the possible chemical interaction of compounds with the main neurotransmitters [17-20].

We perform an analysis of the ACys to know how they affect human body functions.
For this, the HYPERCHEM quantum interaction program is used, which is a quantum analysis tool to compare compounds in pairs using their chemical characteristics [21-24].

2. MATERIALS AND METHODS

This article was evaluated by researchers for three different types of ACys most commonly used as drugs against different types of cancer. The neurotransmitters that we choose for this analysis are the most representative.

It selected specific parameters for each of the simulations shows in Table 1 and 2[26].

Table 1. Parameters used for quantum computing molecular orbitals HOMO and LUMO and BG


Parameter Value Parameter Value
Total Charge 0 Polarizability Not
Spin Multiplicity 1 Geometry Optimization: Algoritm Polak-Ribiere (Conjugated gradient)
Spin Pairing RHF Termination condition RMS gradient of 0.1 kcal/Amol
State Lowest Converget Limit 0.01 Termination condition or 195 maximum cycles
Interation Limit 50 Termination condition or In vacuo
Accelerate Convergence Yes Screen refresh period 1 cyclest

Table 2. Parameters used for quantum computing E-, E+ and EP


Parameter Value Parameter Value
Molecular Property Property Electrostatic Potential Contour Grid Increment 0.05
Representation 3D Mapped Isosurface Mapped Function Options Default
Isosurface Grid: Grid Mesh Size Coarse Transparency level A criteria
Isosurface Grid: Grid Layaout Default Isosurface Rendering: Total charge density contour value 0.015
Contour Grid: Starting Value Default Rendering Wire Mesh Default

3. RESULTS AND DISCUSSION

Table 3 shows the interactions of all the pure substances selected for this study. It can be seen that DAUNORUBICIN is the most chemically stable drug; while ACETYLCHOLINE is the most unstable NT of all of them.

In ascending order, greater stability is noted in the EPIRUBICIN than in the DOXORUBICIN. However, ADRENALINE is interspersed among the three drugs. For this reason, it is assumed that ADRENALINE can be attacked by them very quickly.

Table 3. ETCs of pure substances. The DAUNORUBICIN is the most stable of all. The ACETYLCHOLINE is the most unstable of all


SUBSTANCE HOMO LUMO BG E- E+ EP ETC
ACETYLCHOLINE -9.242 1.034 10.276 -0.028 0.105 0.133 77.265
NORADRENALINE -9.152 -0.004 9.148 -0.083 -0.222 0.139 65.810
GLUTAMIC ACID -10.044 0.537 10.582 -0.084 0.197 0.281 37.657
ASPARTIC ACID -10.242 0.516 10.758 -0.109 0.198 0.307 35.042
GLYCINE -9.853 0.874 10.727 -0.126 0.188 0.314 34.164
GABA -9.562 0.939 10.500 -0.140 0.180 0.320 32.813
DOPAMINE -8.868 0.199 9.067 -0.098 0.189 0.287 31.591
SEROTONINE -8.948 -0.129 8.819 -0.145 0.141 0.286 30.836
DOXORUBICIN* -9.299 -0.605 8.694 -0.115 0.186 0.301 28.885
ADRENALIN -8.998 0.092 9.090 -0.117 0.198 0.315 28.858
EPIRUBICIN* -8.932 -1.235 7.696 -0.109 0.187 0.296 26.000
DAUNORUBICIN* -8.955 -1.293 7.662 -0.137 0.188 0.325 23.575

*The drugs that interact with NTs.


In table 4 we can see the molecule-to-molecule interactions of drugs and NTs. It is important to note that the interactions of the three drugs show a similar pattern. It can be seen in this table that the medicines oxidize the NT with a very high probability. However, NTs have a very low likelihood of oxidizing all three drugs.

We designed, figures 1, 2, 3, and four were to clarify with more precision this event; They illustrate a similar pattern where each NT gives electrons to drugs. Serotonin is the most affected by drugs, then followed by GABA, ADRENALINE, DOPAMINE, GLYCINE.

On the other hand, some interactions between drugs are observed. These undesired interactions may cause a potential deficiency or an increase in the potential of the drugs for their therapeutic effect or their unwanted side reactions (interactions: 60, 54, 53, 49 table 4)


Figure 1. The scheme that shows the jump of electrons or electronic clouds from serotonin to the three drugs.Interactions: 59, 62 and 63 of table 4. This figure represents the oxidation of SEROTONINE by the three drugs



Figure 2. Scheme that shows the jump of electrons or electronic clouds from GABA to the three drugs. Interactions:58, 56 and 45 of table 4. This figure represents the oxidation of GABA by the three drugs



Figure 3. Scheme that shows the jump of electrons or electronic clouds from ADRENALIN to the three drugs. Interactions: 57, 55 and 43 of table 4. This figure represents the oxidation of ADRENALIN by the three drugs



Figure 4. Scheme that shows the jump of electrons or electronic clouds from DOPAMINE to the three drugs. Interactions: 50, 48 and 36 of table 4. This figure represents the oxidation of DOPAMINE by the three drugs


SEROTONIN is known as a very important NT and is related to the state of mind that a person can adopt. There may be a depressive effect in patients who undergo treatment with the 3 drugs. Similarly, ADRENALIN is one of the best known NT and is responsible for increasing the metabolism and alerting it if there is any danger. When interacting with this tree, it could cause a deficit of energy in the patients that would lead to low levels of metabolism in the body. On the other hand, GABA affects the nervous system, which corroborates the above.

Table 4. The ETCs or crossed bands. It is observed that the NT most oxidized by th drug DAUNORUBICIN is the serotonin

  SUBSTANCE  
No REDUCING AGENT OXIDIZING AGENT HOMO LUMO BG E- E+ EP ETC
1

 DAUNORUBICIN NORADRENALINE -8.955 -0.004 8.951 -0.137 -0.222 0.085 105.303
2 DOXORUBICIN NORADRENALINE -9.299 -0.004 9.295 -0.115 -0.222 0.107 86.870
3 EPIRUBICIN NORADRENALINE -8.932 -0.004 8.927 -0.109 -0.222 0.113 79.003
4 DOXORUBICIN ACETYLCHOLINE -9.299 1.034 10.334 -0.115 0.105 0.220 46.971
5 EPIRUBICIN ACETYLCHOLINE -8.932 1.034 9.966 -0.109 0.105 0.214 46.569
6 DAUNORUBICIN ACETYLCHOLINE -8.955 1.034 9.989 -0.137 0.105 0.242 41.278
7 ACETYLCHOLINE DOXORUBICIN -9.242 -0.605 8.637 -0.028 0.186 0.214 40.360
8 ACETYLCHOLINE EPIRUBICIN -9.242 -1.235 8.007 -0.028 0.187 0.215 37.240
9 ACETYLCHOLINE DAUNORUBICIN -9.242 -1.293 7.949 -0.028 0.188 0.216 36.800
10 DOXORUBICIN SEROTONINE -9.299 -0.129 9.170 -0.115 0.141 0.256 35.820
11 EPIRUBICIN SEROTONINE -8.932 -0.129 8.802 -0.109 0.141 0.250 35.209
12 GLUTAMIC ACID DOXORUBICIN -10.044 -0.605 9.439 -0.084 0.186 0.270 34.961
13 DOXORUBICIN GABA -9.299 0.939 10.238 -0.115 0.180 0.295 34.705
14 EPIRUBICIN GABA -8.932 0.939 9.870 -0.109 0.180 0.289 34.153
15 DOXORUBICIN GLYCINE -9.299 0.874 10.174 -0.115 0.188 0.303 33.577
16 EPIRUBICIN GLYCINE -8.932 0.874 9.806 -0.109 0.188 0.297 33.017
17 ASPARTIC ACID DOXORUBICIN -10.242 -0.605 9.637 -0.109 0.186 0.295 32.667
18 GLUTAMIC ACID EPIRUBICIN -10.044 -1.235 8.809 -0.084 0.187 0.271 32.505
19 GLUTAMIC ACID DAUNORUBICIN -10.044 -1.293 8.751 -0.084 0.188 0.272 32.173
20 NORAADRENALINE DOXORUBICIN -9.152 -0.605 8.547 -0.083 0.186 0.269 31.772
21 DAUNORUBICIN SEROTONINE -8.955 -0.129 8.826 -0.137 0.141 0.278 31.747
22 DOXORUBICIN GLUTAMIC ACID -9.299 0.537 9.836 -0.115 0.197 0.312 31.527
23 DOXORUBICIN ASPARTIC ACID -9.299 0.516 9.816 -0.115 0.198 0.313 31.359
24 DOXORUBICIN DOPAMINA -9.299 0.199 9.498 -0.115 0.189 0.304 31.244
25 DAUNORUBICIN GABA -8.955 0.939 9.894 -0.137 0.180 0.317 31.210
26 EPIRUBICIN GLUTAMIC ACID -8.932 0.537 9.469 -0.109 0.197 0.306 30.943
27 EPIRUBICIN ASPARTIC ACID -8.932 0.516 9.448 -0.109 0.198 0.307 30.774
28 EPIRUBICIN DOPAMINA -8.932 0.199 9.130 -0.109 0.189 0.298 30.639
29 ASPARTIC ACID EPIRUBICIN -10.242 -1.235 9.006 -0.109 0.187 0.296 30.427
30 DAUNORUBICIN GLYCINE -8.955 0.874 9.829 -0.137 0.188 0.325 30.245
31 ASPARTIC ACID DAUNORUBICIN -10.242 -1.293 8.949 -0.109 0.188 0.297 30.130
32 DOXORUBICIN ADRENALIN -9.299 0.092 9.391 -0.115 0.198 0.313 30.003
33 GLYCINE DOXORUBICIN -9.853 -0.605 9.248 -0.126 0.186 0.312 29.641
34 EPIRUBICIN ADRENALIN -8.932 0.092 9.023 -0.109 0.198 0.307 29.392
35 NORAADRENALINE EPIRUBICIN -9.152 -1.235 7.916 -0.083 0.187 0.270 29.320
36 DOPAMINE DOXORUBICIN -8.868 -0.605 8.263 -0.098 0.186 0.284 29.094
37 NORAADRENALINE DAUNORUBICIN -9.152 -1.293 7.859 -0.083 0.188 0.271 28.998
38** DOXORUBICIN DOXORUBICIN -9.299 -0.605 8.694 -0.115 0.186 0.301 28.885
39 DAUNORUBICIN GLUTAMIC ACID -8.955 0.537 9.492 -0.137 0.197 0.334 28.420
40 DAUNORUBICIN ASPARTIC ACID -8.955 0.516 9.471 -0.137 0.198 0.335 28.272
41 EPIRUBICIN DOXORUBICIN -8.932 -0.605 8.327 -0.109 0.186 0.295 28.226
42 DAUNORUBICIN DOPAMINA -8.955 0.199 9.154 -0.137 0.189 0.326 28.079
43 ADRENALIN DOXORUBICIN -8.998 -0.605 8.393 -0.117 0.186 0.303 27.701
44 GLYCINE EPIRUBICIN -9.853 -1.235 8.618 -0.126 0.187 0.313 27.532
45 GABA DOXORUBICIN -9.562 -0.605 8.957 -0.140 0.186 0.326 27.474
46 GLYCINE DAUNORUBICIN -9.853 -1.293 8.560 -0.126 0.188 0.314 27.260
47 DAUNORUBICIN ADRENALIN -8.955 0.092 9.047 -0.137 0.198 0.335 27.005
48 DOPAMINE EPIRUBICIN -8.868 -1.235 7.632 -0.098 0.187 0.285 26.780
49 DOXORUBICIN EPIRUBICIN -9.299 -1.235 8.064 -0.115 0.187 0.302 26.702
50 DOPAMINE DAUNORUBICIN -8.868 -1.293 7.575 -0.098 0.188 0.286 26.484
51 DOXORUBICIN DAUNORUBICIN -9.299 -1.293 8.006 -0.115 0.188 0.303 26.423
52** EPIRUBICIN EPIRUBICIN -8.932 -1.235 7.696 -0.109 0.187 0.296 26.000
53 DAUNORUBICIN DOXORUBICIN -8.955 -0.605 8.350 -0.137 0.186 0.323 25.851
54 EPIRUBICIN DAUNORUBICIN -8.932 -1.293 7.638 -0.109 0.188 0.297 25.718
55 ADRENALIN EPIRUBICIN -8.998 -1.235 7.763 -0.117 0.187 0.304 25.536
56 GABA EPIRUBICIN -9.562 -1.235 8.326 -0.140 0.187 0.327 25.462
57 ADRENALIN DAUNORUBICIN -8.998 -1.293 7.705 -0.117 0.188 0.305 25.263
58 GABA DAUNORUBICIN -9.562 -1.293 8.268 -0.140 0.188 0.328 25.208
59 SEROTONINE DOXORUBICIN -8.948 -0.605 8.343 -0.145 0.186 0.331 25.207
60 DAUNORUBICIN EPIRUBICIN -8.955 -1.235 7.720 -0.137 0.187 0.324 23.826
61** DAUNORUBICIN DAUNORUBICIN -8.955 -1.293 7.662 -0.137 0.188 0.325 23.575
62 SEROTONINE EPIRUBICIN -8.948 -1.235 7.713 -0.145 0.187 0.332 23.232
63 SEROTONINE DAUNORUBICIN -8.948 -1.293 7.655 -0.145 0.188 0.333 22.988

** The drugs that interact with NTs. These interactions mark the limits for electron transfer. All the interactions below them have a high probability that they can be carried out.

4. CONCLUSIONS

We studied the interactions between NTs and three ACys.

We found that the interactions NTs vs. ACys have a very similar pattern in all of them.

The ACys always oxidize the NTs.

We found that SEROTONINE is the most affected of the NTs that were studied.

Our findings coincide with the medical literature of the side effects of these three drugs when used to treat any disease.

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