METHYLCYTISINE ALCALOID POTENTIALLY ACTIVE AGAINST DENGUE VIRUS: A MOLECULAR DOCKING STUDY AND ELECTRONIC STRUCTURAL CHARACTERIZATION

Francisco Nithael Melo Lucio; José Elieudo da Silva; Emanuelle Machado Marinho; Francisco Rogênio Da Silva Mendes; Marcia Machado Marinho; Emmanuel Silva Marinho

doi:10.29121/granthaalayah.v8.i1.2020.270

Authors

Francisco Nithael Melo Lucio Chemistry Department, State University of Ceará, Brazil
José Elieudo da Silva Chemistry Department, State University of Ceará, Brazil
Emanuelle Machado Marinho Department of Analytical Chemistry and Physical-Chemistry, Federal University of Ceará, Brazil
Francisco Rogênio Da Silva Mendes Chemistry Department, State University of Ceará, Brazil
Marcia Machado Marinho Department of Clinical and Toxicological Analysis, Federal University of Ceará, Brazil
Emmanuel Silva Marinho Chemistry Department, State University of Ceará, Brazil

DOI:

https://doi.org/10.29121/granthaalayah.v8.i1.2020.270

Keywords:

Alkaloid, Dengue Fever, Docking Molecular, Frontier Orbitals, Human Neuronal Acetylcholine Receptors, Natural Insecticide

Abstract [English]

Dengue fever is a serious disease acquired from the Aedes aegypti mosquito present in tropical and subtropical regions, deeply impacting the population's quality of life. Its control requires combating the virus, and the use of substances that do not cause damage to the environment is of fundamental importance. The present work was carried out in silico to perform the structural-electronic characterization of the alkaloid Methylcytisine, a tricyclic quinolizidine alkaloid that has insecticidal activities, identifying the molecular boundary orbitals and descriptors of global chemical reactivity and assessing the inhibitory potential of methylcytisine on NS5 methyltransferase enzyme dengue virus, as well as identifying possible biological targets in humans. Methylcytisine was geometrically optimized through semi-empirical quantum calculations with thermodynamically more stable conformation, characterizing its structure (atoms, angles and bonds) and its reactivity descriptors. The analysis of the molecular docking simulations showed that methylcytisine is coupled in the same active site of the NS5 enzyme methyltransferase DENV, very similar to the complexed ligand S-adenosyl-L-homocysteine. The intermolecular interactions found for the complex formed and the distance values of the enzyme residues, indicate that methylcytisine has potential application as a new inhibitor of the dengue virus, however it has a high possibility of interaction with human neuronal acetylcholine receptors.

Downloads

Download data is not yet available.

References

M. D. G. Teixeira, M. L. Barreto, and Z. Guerra, “Epidemiologia e Medidas de Prevenção do Dengue,” Inf. epidemiológico do SUS, vol. 8, no. 4, pp. 5–33, 1999.

S. Singhi, N. Kissoon, and A. Bansal, “Dengue e dengue hemorrágico: Aspectos do manejo na unidade de terapia intensiva,” J. Pediatr. (Rio. J)., vol. 83, no. SUPPL. 2, pp. 22–35, 2007. DOI: https://doi.org/10.1590/S0021-75572007000300004

M. De Freitas Lenzi and L. Camillo Coura, “Prevenção da dengue: A informação em foco,” Rev. Soc. Bras. Med. Trop., vol. 37, no. 4, pp. 343–350, 2004. DOI: https://doi.org/10.1590/S0037-86822004000400011

M. Dos Santos, A. C. DOS SANTOS PEREIRA ANDRADE, A. A. ALEIXO, R. J. ALVES, A. C. DE OLIVEIRA BRETAS, and J. M. SIQUEIRA FERREIRA, “Avaliação da citotoxicidade de compostos sintéticos como potenciais fármacos contra Dengue vírus,” BBR - Biochem. Biotechnol. Reports, vol. 2, no. 2esp, p. 57, 2013. DOI: https://doi.org/10.5433/2316-5200.2013v2n2espp57

F. P. Lobo et al., “Virus-host coevolution: Common patterns of nucleotide motif usage in Flaviviridae and their hosts,” PLoS One, 2009. DOI: https://doi.org/10.1371/journal.pone.0006282

A. R. Lima, J. Silva, L. L. Bezerra, M. M. Marinho, and E. S. Marinho, “Molecular docking of potential curcuminoids inhibitors of the NS1 protein of dengue virus,” Int. J. Sci. Eng. Res., vol. 8, no. 4, 2017.

F. Martins, P. Sérgio, B. De Lacerda, and J. Junior, “Divulgação,” vol. 28, no. 1, pp. 103–110, 2005. DOI: https://doi.org/10.1590/S0100-40422005000100019

J. C. R. Corrêa and H. R. N. Salgado, “Atividade inseticida das plantas e aplicações: Revisão,” Revista Brasileira de Plantas Medicinais. 2011. DOI: https://doi.org/10.1590/S1516-05722011000400016

Y. F. Jiao et al., “N-methylcytisine ameliorates dextran-sulfate-sodium-induced colitis in mice by inhibiting the inflammatory response,” Molecules, vol. 23, no. 3, pp. 1–14, 2018. DOI: https://doi.org/10.3390/molecules23030510

K. Matsuda, M. Kimura, K. Komai, and M. Hamada, “Nematicidal Activities of (-)-N-Meth ylcytisine and (-)-Anagyrine from Sophora flavescens against Pine Wood Nematodes,” Agric. Biol. Chem., vol. 53, no. 8, pp. 2287–2288, 1989. DOI: https://doi.org/10.1080/00021369.1989.10869614

I. CARVALHO, M. T. PUPO, and L. S. C. BORGES, Á. D. L. BERNARDES, “Introdução a modelagem molecular de fármacos no curso experimental de química farmacêutica,” Quim. Nova, vol. 23, pp. 428–438, 2003. DOI: https://doi.org/10.1590/S0100-40422003000300023

E. J. Braga, B. T. Corpe, M. M. Marinho, and E. S. Marinho, “Molecular electrostatic potential surface, HOMO–LUMO, and computational analysis of synthetic drug Rilpivirine,” Int. J. Sci. Eng. Res., vol. 7, no. 7, pp. 315–319, 2016.

S. S. Carneiro, A. R. Lima, M. M. Marinho, and E. S. Marinho, “In silico Study Of The Therapeutic Agent In The Treatment Of Non-Hodgkin ’ s Lymphomas , Peripheral T- Cell Belinostat , A Semi-Empirical Approach,” Imp. J. Interdiscip. Res., no. 8, pp. 1645–1648, 2016.

E. J. Barreiro, C. R. Rodrigues, M. G. Albuquerque, C. M. R. de Sant’Anna, and R. B. de Alencastro, “Modelagem Molecular: Uma Ferramenta para o Planejamento Racional de Fármacos em Química Medicinal,” Quim. Nova, vol. 20, no. 3, pp. 300–310, 1997. DOI: https://doi.org/10.1590/S0100-40421997000300011

S. S. Carneiro et al., “Study of the interactional properties between Curcumin / Monodimethylcurcumin andprotein (NS1) of dengue fever virus type 4 (DENV4),” Int. J. Sci. Eng. Res. Vol., vol. 8, no. 7, pp. 2238–2243, 2017.

M. M. Marinho et al., “MOLECULAR FRACTIONATION WITH CONJUGATE CAPS STUDY OF THE INTERACTION OF THE ANACARDIC ACID WITH THE ACTIVE SITE OF TRYPANOSOMA CRUZI GAPDH ENZYME : A QUANTUM INVESTIGATION,” Asian J Pharm Clin Res, vol. 12, no. 12, 2019.

H. Lucas et al., “In silico study of the drug oseltamivir and its interactions with influenza hemagglutinins 5C0r and 5C0s,” Int. J. Sci. Eng. Res., vol. 9, no. 3, pp. 1196–1202, 2018. DOI: https://doi.org/10.14299/ijser.2018.03.05

S. P. Estácio, M. M. Marinho, and E. S. Marinho, “Use of Classic Force Field Mmff94 for Conformational Characterization of Antihypertensive Drug Sacubitril,” vol. XI, no. 4, pp. 13–19, 2018.

M. Reges, M. M. Marinho, and E. S. Marinho, “In Silico Characterization of Hypoglycemic Agent Phenformin Using Classical Force Field MMFF94,” Int. J. Recent Res. Rev., vol. XI, no. 2, pp. 36–43, 2018.

L. Cláudio, M. M. Marinho, and E. Silva, “In Silico Study of Antiparkinson Drug Levodopa and Drug Design of Four Theoretical Analogues,” Int. J. Recent Res. Rev., vol. X, no. 4, pp. 24–28, 2017.

James J. P. Stewart, “No Title,” J. Comp. Chem, vol. 10, pp. 209–220, 1989. DOI: https://doi.org/10.1002/jcc.540100208

J. J. P. Stewart, “No Title,” J. Comp. Chem, vol. 10, pp. 221–264, 1989. DOI: https://doi.org/10.1002/jcc.540100209

S. Joy, P. Nair, R. Hariharan, and M. Pillai, “Detailed comparison of the protein-ligand docking efficiencies of GOLD, a commercial package and ArgusLab, a licensable freeware,” In Silico Biol., vol. 6, pp. 601–605, Feb. 2006.

M. Reges, M. M. Marinho, and E. S. Marinho, “Structural Characterization of the Hypoglycemic Drug Glimepiride,” Int. J. Recent Res. Rev., vol. XI, no. 2, pp. 26–35, 2018.

and G. K. S. J. P. M. A. Thompson, “No Title,” Chem, vol. 99, pp. 6374–6386, 1995. DOI: https://doi.org/10.1021/j100017a017

M. A. Thompson, “Planaria Software LLC, Seattle, WA.” .

D. Lopes et al., “IN SILICO STUDIES OF SOPHORAFLAVANONE G : QUANTUM,” Int. J. Res. - GRANTHAALAYAH, vol. 7, no. November, pp. 160–179, 2019. DOI: https://doi.org/10.29121/granthaalayah.v7.i11.2020.347

E. S. Marinho, “UTILIZAÇÃO DO MÉTODO SEMI-EMPÍRICO PM7 PARA CARACTERIZAÇÃO DO FÁRMACO ATALURENO : HOMO ,” Rev. Expressão Católica, vol. 1, no. 1, pp. 177–184, 2016. DOI: https://doi.org/10.25191/recs.v1i1.1393

T. Koopmans, “Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms,” Physica, 1934. DOI: https://doi.org/10.1016/S0031-8914(34)90011-2

V. M. De Oliveira, M. M. Marinho, and E. S. Marinho, “Semi-Empirical Quantum Characterization of the Drug Selexipag : HOMO and LUMO and Reactivity Descriptors,” Int. J. Recent Res. Rev., vol. XII, no. 2, pp. 15–20, 2019.

M. P. Egloff, D. Benarroch, B. Selisko, J. L. Romette, and B. Canard, “An RNA cap (nucleoside-2′-O-)-methyltransferase in the flavivirus RNA polymerase NS5: Crystal structure and functional characterization,” EMBO J., vol. 21, no. 11, pp. 2757–2768, 2002. DOI: https://doi.org/10.1093/emboj/21.11.2757

O. Trott and A. Olson, “Autodock vina: improving the speed and accuracy of docking,” J. Comput. Chem., vol. 31, no. 2, pp. 455–461, 2010.

E. F. Pettersen et al., “UCSF Chimera - A visualization system for exploratory research and analysis,” J. Comput. Chem., vol. 25, no. 13, pp. 1605–1612, 2004. DOI: https://doi.org/10.1002/jcc.20084

C. Modeling and F. O. R. L. Sciences, “Biovia Discovery Studio ® 2016 Comprehensive Modeling and Simulations,” 2016.

D. Gfeller, O. Michielin, and V. Zoete, “Shaping the interaction landscape of bioactive molecules,” Bioinformatics, 2013. DOI: https://doi.org/10.1093/bioinformatics/btt540

D. Gfeller, A. Grosdidier, M. Wirth, A. Daina, O. Michielin, and V. Zoete, “SwissTargetPrediction: A web server for target prediction of bioactive small molecules,” Nucleic Acids Res., 2014. DOI: https://doi.org/10.1093/nar/gku293

D. Lopes, S. De Oliveira, M. M. Marinho, and E. S. Marinho, “Characterization in Silic of Anti-Epiletic Drug ( 2S ) -2- [( 4R )-2- Oxo-4-propylpyrrolidin-1-yl Butanamide,” Int. J. Recent Res. Rev., vol. XI, no. 4, pp. 5–12, 2018.

E. S. Marinho, “A DFT study of synthetic drug topiroxostat: MEP, HOMO, LUMO,” Int. J. Sci. Eng. Res., vol. 7, no. July, pp. 1264–1270, 2016.

R. B. de A. E. J. Barreiro, C. R. Rodrigues, M. G. Albuquerque, C. M. R. de Sant’anna, “Molecular Modeling: A Tool for the Rational Planning of Drugs in Medicinal Chemistry,” New Chem., vol. 20, p. 1, 1997.

S. S. Carneiro, M. M. Marinho, and E. S. Marinho, “Electronic / Structural Characterization of Antiparkinsonian Drug Istradefylline : A Semi-Empirical Study,” Int. J. Recent Res. Rev., vol. X, no. 4, pp. 9–14, 2017.

M. Aurélio, C. De Oliveira, M. M. Marinho, and S. Marinho, “UTILIZAÇÃO DO MÉTODO QUÂNTICO PM7 PARA CARACTERIZAÇÃO DO ROTENOIDE DEGUELINA : UM AGENTE CONTRA O AEDES AEGYPTI,” JOIN, no. 1, 2017.

D. H. Pereira, F. A. La Porta, R. T. Santiago, D. R. Garcia, and T. C. Ramalho, “New perspectives on the role of frontier molecular orbitals in the study of chemical reactivity: A review,” Rev. Virtual Quim., 2016. DOI: https://doi.org/10.5935/1984-6835.20160032

C. B. Zhang, G., & Musgrave, “Comparison of DFT methods for molecular orbital eigenvalue calculations,” J. Phys. Chem. A, vol. 111, pp. 1554–1561, 2007. DOI: https://doi.org/10.1021/jp061633o

D. J. Tozer and N. C. Handy, “Improving virtual Kohn-Sham orbitals and eigenvalues: Application to excitation energies and static polarizabilities,” J. Chem. Phys., 1998. DOI: https://doi.org/10.1063/1.477711

E. S. M. G. A. Araújo, E. P. Silva, E. P. Sanabio, J. A. Pinheiro, R.R. Castro, R.R. Castro, M.M. Marinho, F. K. S.Lima, “Characterization in Silico of the Structural Parameters of the Antifungal Agent Ketoconazole,” Sci. Signpost Publ., 2016.

L. Paes, W. L. Santos, and M. M. Marinho, “MESP E MULLIKEN,” no. September 2019, 2017.

L. Paes, W. L. Santos, M. M. Marinho, and E. S. Marinho, “ESTUDO DFT DO ALCALOIDE DICENTRINA: GAP, HOMO, LUMO, MESP E MULLIKEN,” JOIN, no. 1, 2017.

J. Silva, A. R. Lima, L. L. Bezerra, M. M. Marinho, and E. S. Marinho, “Bixinoids potentially active against dengue virus: a molecular docking study,” JInternational J. Sci. Eng. Res., vol. 8, no. 4, pp. 882–887, 2017.

L. L. Bezerra;, J. Silva, A. R. Lima;, C. L. de M. Filho;, M. M. Marinho;, and E. S. Marinho, “DOCKING MOLECULAR STUDIES BETWEEN THE BIXIN AND NORBIXIN CAROTENOIDS AND THE DENGUE FEVER VIRUS (NS1),” Int. J. Sci. Eng. Res. Vol., vol. 8, no. 11, pp. 520–526, 2017.

J. Silva, M. M. Marinho, and E. S. Marinho, “ESTUDOS DE ACOPLAMENTO MOLECULAR ENTRE O LIGANTE β - BIXINA E A PROTEÍNA NS1 DO VÍRUS DA DENGUE,” JOIN, no. 1, 2017.

[J. Silva, M. M. Marinho, J. E. da Silva, E. M. Marinho, and E. S. Marinho, “Estudo Comparativo De Docking Molecular Entre O Inibidor De Protease Saquinavir E O Carotenoide Bixina Como Potencial Inibidor Do Vírus Hiv Tipo I (1Hxb),” Rev. Expressão Católica Saúde, vol. 3, no. 1, p. 35, 2018. DOI: https://doi.org/10.25191/recs.v3i1.2223

[S. A. De Alencar, “Utilização de ferramentas computacionais para o estudo do impacto funcional e estrutural de nsSNPs em genes codificadores de proteínas,” 2010.

A. R. Lima and E. S. Marinho, “Alicina uma potencial aliada contra a Chikungunya ( CHIKV ): um estudo de docking molecular,” An. do XXIII Encontro Iniciac. a Pesqui. -UNIFOR, vol. 3, 2017.

L. L. Bezerra, M. M. Marinho, E. S. Marinho, M. Reges, M. M. Marinho, and E. S. Marinho, “Molecular Docking Studies Between Anthraquinone Aloe Emodin and Dengue Virus Protein ( Denv-2 ),” Int. J. Recent Res. Rev., vol. XI, no. 1, pp. 14–18, 2018.

E. Yuriev, J. Holien, and P. A. Ramsland, “Improvements, trends, and new ideas in molecular docking: 2012–2013 in review,” J. Mol. Recognit., vol. 28, pp. 581–606, 2015. DOI: https://doi.org/10.1002/jmr.2471

S. Shityakov and C. Förster, “In silico predictive model to determine vector-mediated transport properties for the blood-brain barrier choline transporter,” Adv. Appl. Bioinforma. Chem., 2014. DOI: https://doi.org/10.2147/AABC.S63749