J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1139-1148, November-December 2022.
DOI: https://doi.org/10.56499/jppres22.1478_10.6.1139
Original Article
Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies
[Potencial de los compuestos ionóforos de poliéter como antimaláricos mediante la inhibición de glutatión S-transferasa de Plasmodium falciparum a través de estudios de acoplamiento molecular]
Alfian Wika Cahyono1,2, Icha Farihah Deniyati Faratisha1, Nabila Erina Erwan1,3, Rivo Yudhinata Brian Nugraha1,4, Ajeng Maharani Putri1,3, Loeki Enggar Fitri1,4*
1Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.
2Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.
3Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.
4Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.
*E-mail: lukief@ub.ac.id
Abstract
Context: Malaria is still a serious global health problem due to the development of drug resistance. It is necessary to find new drugs with renewable mechanisms that are effective in killing parasites. Our previous research has analyzed more than one compound of polyether ionophore group in ethyl acetate Streptomyces hygroscopicus subsp. hygroscopicus extract. Polyether ionophore is known to have a similar mechanism of action to chloroquine which is potent in inhibiting Plasmodium falciparum glutathione S-transferase (PfGST).
Aims: To evaluate the potential effect of polyether ionophore toward PfGST as a target protein through molecular docking.
Methods: PfGST was obtained from Protein Data Bank. Test ligands (polyether ionophore) and control ligands (chloroquine) were obtained from PubChem. Pharmacokinetic analysis was done using SwissADME, molecular docking using PyRx 0.9, visualization using LigPlot and PyMOL, and molecular dynamics using YASARA for the best ligand activity.
Results: Lenoremycin had the highest binding affinity to PfGST (-8.53 kcal/mol) among other polyether ionophores, and nigericin had the best residue bonding with hydrophobic and hydrogen with a binding affinity of -8.25 kcal/mol compared to chloroquine complex in molecular docking and molecular dynamic simulation.
Conclusions: Polyether ionophore could serve as an antimalarial agent better than chloroquine, with nigericin as the best compound candidate in inhibiting PfGST compared to other polyether ionophores.
Keywords: malaria; molecular docking; PfGST; polyether ionophore; Streptomyces hygroscopicus.
Resumen
Contexto: La malaria sigue siendo un grave problema sanitario mundial debido al desarrollo de resistencia a los fármacos. Es necesario encontrar nuevos fármacos con mecanismos renovables que sean eficaces para matar a los parásitos. Nuestra investigación anterior ha analizado más de un compuesto del grupo ionóforo poliéter en el extracto de acetato de etilo de Streptomyces hygroscopicus subsp. hygroscopicus. Se sabe que el poliéter ionóforo tiene un mecanismo de acción similar al de la cloroquina, que es potente inhibidor de la gutatión S-transferasa de Plasmodiun falciparum (PfGST).
Objetivos: Evaluar el efecto potencial del poliéter ionóforo hacia la PfGST como proteína diana a través del acoplamiento molecular.
Métodos: PfGST se obtuvo del Banco de Datos de Proteínas. Los ligandos de prueba (poliéter ionóforo) y los ligandos de control (cloroquina) se obtuvieron de PubChem. El análisis farmacocinético se realizó con SwissADME, el docking molecular con PyRx 0.9, la visualización con LigPlot y PyMOL, y la dinámica molecular con YASARA para la mejor actividad del ligando.
Resultados: La lenoremycina tuvo la mayor afinidad de unión a PfGST (-8,53 kcal/mol) entre otros poliéteres ionóforos, y la nigericina tuvo la mejor unión de residuos con hidrófobos e hidrógenos con una afinidad de unión de -8,25 kcal/mol en comparación con el complejo de cloroquina en el docking molecular y la simulación dinámica molecular.
Conclusiones: El ionóforo poliéter podría servir como agente antimalárico mejor que la cloroquina, siendo la nigericina el mejor candidato para inhibir el PfGST en comparación con otros ionóforos poliéter.
Palabras Clave: acoplamiento molecular; ionóforo poliéter; malaria; PfGST; Streptomyces hygroscopicus.
Citation Format: Cahyono AW, Faratisha IFD, Erwan NE, Nugraha RYB, Putri AM, Fitri LE (2022) Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies. J Pharm Pharmacogn Res 10(6): 1139–1148. https://doi.org/10.56499/jppres22.1478_10.6.1139
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