Tag Archives: molecular docking

Virtual screening of lead flavonoids against DENV2

J. Pharm. Pharmacogn. Res., vol. 10, no. 4, pp. 660-675, July-August 2022.

Original Article

Flavonoids as potential inhibitors of dengue virus 2 (DENV2) envelope protein

[Flavonoides como posibles inhibidores de la proteína de la cubierta del virus del dengue 2 (DENV2)]

Rachel Raditya Renantha1, Alvin Richardo Liga1, Christy Bianca Tanugroho1, Lovine Xaviera Denovian1, Siti Lateefa Az Zahra Budiyanto2, Arli Aditya Parikesit2*

1Department of Biomedicine, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav.88 Jakarta 13210 Indonesia.

2Department of Bioinformatics, School of Life Sciences, Indonesia International Institute for Life Sciences, Jl. Pulomas Barat Kav.88 Jakarta 13210 Indonesia.

*E-mail: arli.parikesit@i3l.ac.id


Context: Dengue viruses (DENVs) are the cause of dengue disease, which is one of the most frequent diseases caused by mosquito-borne viral infections. Currently, no specific treatment is available for dengue.

Aims: To identify the most promising inhibitors of dengue virus 2 (DENV2) envelope protein of DENV2 envelope protein from flavonoids compounds through computational methods.

Methods: Structures of 54 flavonoids were collected, then the compounds were screened based on Lipinski’s rules, and there were only 34 compounds that passed the screening. Then QSAR analysis was performed, followed by molecular docking analysis, ADMET evaluation, and molecular dynamics simulations to assess the stability of the protein.

Results: Based on the QSAR analysis, only 32 compounds were subjected to molecular docking analysis. Silymarin had the highest docking score, while juglanin had the lowest ACE score compared to positive controls. The ADMET evaluation showed silymarin and juglanin had good absorption and could not penetrate the blood-brain barrier. In contrast to silymarin which had negative results for the Ames test, carcinogenicity, skin sensitization, and eye irritation, juglanin was positive for Ames test and skin sensitization. Even though the molecular dynamic simulation of both ligands with DENV2 envelope protein showed unstable confirmation, it did not necessarily mean that the ligands cannot be used as inhibitors since the molecular docking results provide evidence of the ligands binding to the DENV2 envelope protein.

Conclusions: Based on the favorable results of QSAR analysis, molecular docking, and ADMET evaluation, juglanin and silymarin were chosen as the candidate with the most potential for DENV2 envelope protein inhibitors. However, further analyses such as in vitro and in vivo analyses are necessary to validate the result of this study.

Keywords: DENV-2; envelope protein; flavonoids; molecular docking; virtual screening.


Contexto: Los virus del dengue (DENV) son los causantes de la enfermedad del dengue, que es una de las enfermedades más frecuentes causada por infecciones virales transmitidas por mosquitos. Actualmente, no se dispone de un tratamiento específico para el dengue.

Objetivos: Identificar los inhibidores más prometedores de la proteína de la envoltura del virus del dengue 2 (DENV2) de la proteína de la envoltura del DENV2 a partir de compuestos de flavonoides a través de métodos computacionales.

Métodos: Las estructuras de 54 flavonoides fueron recolectadas. Los compuestos se seleccionaron según las reglas de Lipinski y solo 34 compuestos pasaron la selección. Luego se realizó el análisis QSAR, seguido de análisis de acoplamiento molecular, evaluación ADMET y simulaciones de dinámica molecular para evaluar la estabilidad de la proteína.

Resultados: Según el análisis QSAR, solo 32 compuestos se sometieron a análisis de acoplamiento molecular. La silimarina obtuvo la puntuación de acoplamiento más alta, mientras que juglanina obtuvo la puntuación ACE más baja en comparación con los controles positivos. La evaluación ADMET mostró que la silimarina y la juglanina tenían una buena absorción y no podían penetrar la barrera hematoencefálica. En contraste con la silimarina que tuvo resultados negativos para la prueba de Ames, carcinogenicidad, sensibilización de la piel e irritación de los ojos, la juglanina fue positiva para la prueba de Ames y la sensibilización de la piel. Aunque la simulación de la dinámica molecular de ambos ligandos con la proteína de la cubierta de DENV2 mostró una confirmación inestable, no significa necesariamente que los ligandos no puedan usarse como inhibidores, ya que los resultados del acoplamiento molecular proporcionan evidencia de que los ligandos se unen a la proteína de la cubierta de DENV2.

Conclusiones: En base a los resultados favorables del análisis QSAR, el acoplamiento molecular y la evaluación ADMET, la juglanina y la silimarina fueron elegidas como las candidatas con mayor potencial para los inhibidores de la proteína de la envoltura de DENV2. Sin embargo, se necesitan más análisis, como análisis in vitro e in vivo, para validar el resultado de este estudio.

Palabras Clave: acoplamiento molecular; DENV-2; flavonoides; proteína de envoltura; proyección virtual.

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Citation Format: Renantha RR, Liga AR, Tanugroho CB, Denovian LX, Budiyanto SLAZ, Parikesit AA (2022) Flavonoids as potential inhibitors of dengue virus 2 (DENV2) envelope protein. J Pharm Pharmacogn Res 10(4): 660–675.

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In-silico study of volatile compounds and COVID-19

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 469-485, May-June 2022.

Original Article

Volatile compounds from Phyla scaberrima (Juss. ex Pers.) Moldenke and Dysphania ambrosioides (L.) Mosyakin & Clemants as possible SARS-CoV-2 protease inhibitors: Identification and in-silico study

[Compuestos volátiles de Phyla scaberrima (Juss. ex Pers.) Moldenke y Dysphania ambrosioides (L.) Mosyakin & Clemants como posibles inhibidores de proteasas de SARS-CoV-2: Identificación y estudio in-silico]

Neyder Contreras-Puentes1*, Manuel Salas-Moreno2,3, Lina Mosquera-Chaverra2, Leonomir Córdoba-Tovar4, Antistio Alviz-Amador5

1GINUMED, Medicine, Corporation University Rafael Nuñez, Cartagena D.T y C, Colombia.

2Faculty of Naturals Sciences, Biology Department, Biosistematic Research Group, Technological University of Chocó, Quibdó, Colombia.

3Analytical Chemistry and Biomedicine Group. Exacts and Natural Sciences Faculty. University of Cartagena. Cartagena, Colombia.

4Research Group Natural Resources and Environmental Toxicology, Technological University of Chocó, Quibdó, Colombia.

 5Pharmacology and Therapeutics Group, University of Cartagena, Cartagena D.T y C., Colombia.

*E-mail: neyder.contreras@curnvirtual.edu.co


Context: COVID-19 is a pandemic that has affected the entire population, characterized by multisystemic involvement. With around 130 million cases of infection and more than 2.5 million deaths globally. However, the development of a low-efficacy treatment has led to the study of natural products as possible therapeutic alternatives against SARS-CoV-2.

Aims: To identify volatile compounds present in two plants in the Colombian Pacific and carry out in-silico studies to search for promising inhibitory molecules against SARS-CoV-2 proteases.

Methods: This research carried out the identification of metabolites of two plants identified in the Colombian Pacific, called P. scaberrima (Juss. ex Pers.) Moldenke y D. ambrosioides (L.) Mosyakin & Clemants. Ethanolic extracts were obtained by rotary-evaporation and determinated by GC-MS. Subsequently, in-silico studies were carried out by molecular docking against Mpro and PLpro using Autodock-vina 1.1. Also, a prediction of ADMET properties using SwissADME and GUSAR-Online server was performed.

Results: Thus, 15 volatile compounds with similarities greater than 85% were identified from both extracts, mostly sesquiterpenic and monoterpenic compounds. The compounds that showed the highest affinity against Mpro were α-amorphene and phytol for PLpro. Likewise, these were contrasted with co-crystallized molecules such as boceprevir and VIR2-251 as control structures. Finally, the predictions of ADMET properties showed values consistent with the literature.

Conclusions: Therefore, the follow-up of in-silico studies with these plants from Colombian pacific are considered as possible tools in the search for active molecules against proteases linked to virus.

Keywords: Dysphania ambrosioides; GC-MS/MS; molecular docking; Phyla scaberrima; SARS-CoV-2.

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Contexto: COVID-19 es una pandemia que ha afectado a toda la población mundial, caracterizada por compromisos multisistémicos. Con alrededor de 130 millones de casos de infección y más de 2,5 millones de muertes en todo el mundo. Sin embargo, el desarrollo de un tratamiento de baja eficacia ha llevado al estudio de productos naturales como posibles alternativas terapéuticas frente al SARS-CoV-2.

Objetivos: Identificar compuestos volátiles presentes en dos plantas del Pacifico colombiano y realizar estudios in-silico para la búsqueda de promisorias moléculas inhibidoras contra proteasas de SARS-CoV-2.

Métodos: En esta investigación se realizó la identificación de metabolitos de dos plantas identificadas en el Pacífico colombiano, llamadas P. scaberrima (Juss. ex Pers.) Moldenke y D. ambrosioides (L.) Mosyakin & ClemantsSe obtuvieron extractos etanólicos, preconcentrados con evaporación rotatoria y se determinaron por GC-MS. Posteriormente, se realizaron estudios in-silico mediante acoplamiento molecular contra Mpro y PLpro utilizando Autodock-vina. Además, prediciendo las propiedades de ADMET mediante SwissADME y GUSAR-Online.

Resultados: Se identificaron 15 compuestos volátiles con similitudes superiores al 85% de ambos extractos, en su mayoría compuestos sesquiterpénicos y monoterpénicos. Los compuestos que mostraron la mayor afinidad contra Mpro fue α-amorfeno y fitol para PLpro. Asimismo, se contrastaron con moléculas co-cristalizadas como boceprevir y VIR2-251 como estructuras control. Finalmente, en las predicciones de propiedades ADMET mostraron valores consistentes con la literatura.

Conclusiones: Se consideró el seguimiento de estudios in-silico con estas plantas del Pacífico colombiano como posibles herramientas en la búsqueda de moléculas activas frente a proteasas ligadas al virus.

Palabras Clave: acoplamiento molecular; Dysphania ambrosioides; GC-MS/MS; Phyla scaberrima; SARS-CoV-2.

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Citation Format: Contreras-Puentes N, Salas-Moreno MH, Mosquera-Chaverra L, Córdoba-Tovar L, Alvíz-Amador AA (2022) Volatile compounds from Phyla scaberrima (Juss. ex Pers.) Moldenke y Dysphania ambrosioides (L.) Mosyakin & Clemants as possible SARS-CoV-2 protease inhibitors: Identification and in-silico study. J Pharm Pharmacogn Res 10(3): 469–485.

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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Roselle flower for immunomodulatory adjuvant therapy in COVID-19

J. Pharm. Pharmacogn. Res., vol. 10, no. 3, pp. 418-428, May-June 2022

Original Article

Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach

[Antocianina, ácido tartárico, ácido ascórbico de flor de Jamaica (Hibiscus sabdariffa L.) para la terapia adyuvante inmunomoduladora en la manifestación oral de la enfermedad por coronavirus-19: Un enfoque inmunoinformático]

Nastiti Faradilla Ramadhani1, Alexander Patera Nugraha1,2*, Desintya Rahmadhani3, Martining Shoffa Puspitaningrum3, Yuniar Rizqianti3, Viol Dhea Kharisma4, Tengku Natasha Eleena binti Tengku Ahmad Noor5, Rini Devijanti Ridwan6, Diah Savitri Ernawati7, Albertus Putera Nugraha8

1Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Department of Orthodontic, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Graduate Student of Biology Science, Department of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Malang, Indonesia

5Military Dental Officer of Royal Medical and Dental Corps, Malaysian Armed Forces, Indonesia.

6Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

7Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

8Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

*E-mail: alexander.patera.nugraha@fkg.unair.ac.id


Context: Oral manifestations that arose from COVID-19 infection often causes morbidity and systemic drug administration is less effective. Roselle flower (Hibiscus sabdariffa) is one of the plants that is often used in infusion as it gives health benefits. Hence, H. sabdariffa may benefit from adjuvant therapy to treat oral manifestation due to COVID-19.

Aims: To investigate the potential of H. sabdariffa anthocyanins, tartaric acid, and ascorbic acid chemical compounds as antiviral, anti-inflammatory, antioxidant, and increasing tissue regeneration in oral manifestation due to COVID-19 infection in silico.

Methods: Chemical compounds consisted of anthocyanins, (+)-tartaric acid, and ascorbic acid beside target proteins consisted of ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR and MDA-ovalbumin were obtained from the database, ligand samples were selected through absorption, distribution, metabolism, excretion and toxicology analysis, then molecular docking simulations, identification of protein-ligand interactions, and 3D visualization were performed.

Results: Anthocyanins, tartaric acid, and ascorbic acid are the active compounds in H. sabdariffa, which act as antioxidants. The activity of anthocyanin compounds is higher than other compounds through value binding affinity, which is more negative and binds to specific domains of target proteins by forming weak binding interactions that play a role in biological responses. Anthocyanins have the most negative binding energy compared to tartaric-acid and ascorbic acid.

Conclusions: Anthocyanins act as antioxidants; this mechanism increases heat shock protein-70 (HSP70), which may play an important role in increasing wound regeneration of oral manifestation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as documented in silico.

Keywords: COVID-19; dentistry; Hibiscus sabdariffa; infectious disease; medicine.


Contexto: Las manifestaciones orales derivadas de la infección por COVID-19 suelen causar morbilidad y la administración sistémica de fármacos es menos efectiva. La flor de Jamaica (Hibiscus sabdariffa) es una de las plantas que se suele utilizar en infusión ya que aporta beneficios para la salud. Por lo tanto, H. sabdariffa puede beneficiarse de la terapia adyuvante para tratar las manifestaciones orales debido a COVID-19.

Objetivos: Investigar el potencial de los compuestos químicos de H. sabdariffa, como antocianinas, ácido tartárico y ácido ascórbico como antivirales, antiinflamatorios, antioxidantes y el aumento de la regeneración de tejidos en la manifestación oral debido a la infección por COVID-19 a través de un enfoque inmunoinformático, un estudio in silico.

Métodos: Antocianinas, ácido tartárico y ácido ascórbico, además de proteínas diana como ACE2-spike, Foxp3, IL-10, IL6, IL1β, VEGF, FGF-2, HSP70, TNFR y MDA-ovoalbúmina, se obtuvieron de la base de datos, las muestras de ligando se seleccionaron mediante análisis de absorción, distribución, metabolismo, excreción y toxicología, luego se realizaron simulaciones de acoplamiento molecular, identificación de interacciones proteína-ligando y visualización 3D.

Resultados: Las antocianinas, el ácido tartárico y el ácido ascórbico son los compuestos activos de H. sabdariffa que actúan como antioxidantes. La actividad de los compuestos de antocianina es mayor que la de otros compuestos a través de una afinidad de unión de valor que es más negativa y se une a dominios específicos de proteínas diana formando interacciones de unión débiles que desempeñan un papel en las respuestas biológicas. Las antocianinas tienen la energía de unión más negativa en comparación con el ácido tartárico y el ácido ascórbico.

Conclusiones: Las antocianinas actúan como antioxidantes; este mecanismo aumenta la proteína de choque térmico-70 (HSP70), que puede desempeñar un papel importante en el aumento de la regeneración de heridas de la manifestación oral en el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) como se documenta in silico.

Palabras Clave: COVID-19; enfermedad infecciosa; Hibiscus sabdariffa; medicamento; odontología.

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Citation Format: Ramadhani NF, Nugraha AP, Rahmadani D, Puspitaningrum MS, Rizqianti Y, Kharisma VD, Noor TNEBTA, Ridwan RD, Ernawati DS, Nugraha AP (2022) Anthocyanin, tartaric acid, ascorbic acid of roselle flower (Hibiscus sabdariffa L.) for immunomodulatory adjuvant therapy in oral manifestation coronavirus disease-19: An immunoinformatic approach. J Pharm Pharmacogn Res 10(3): 418–428.

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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Moroccan medicinal plants against COVID-19

J Pharm Pharmacogn Res 10(2): 227-238, 2022.

Original Article

Molecular docking study of the main phytochemicals of some medicinal plants used against COVID-19 by the rural population of Al-Haouz region, Morocco

[Estudio de acoplamiento molecular de los principales fitoquímicos de algunas plantas medicinales utilizadas contra el COVID-19 por la población rural de la región de Al-Haouz, Marruecos]

Ridwane Ghanimi1*, Ahmed Ouhammou2, Yassine El Atki3, Mohamed Cherkaoui1

1Laboratory of Pharmacology, Neurobiology, Anthropobiology, Environment and Behaviour, Department of Biology, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, BP 2390, 40000, Morocco.

2Laboratory of Microbial Biotechnologies, Agrosciences and Environment (BioMAgE), Agrosciences, Phytobiodiversity and Environment Team, Regional Herbarium ‘MARK’, Department of Biology, Faculty of Sciences Semlalia , Cadi Ayyad University, PO. Box 2390, Marrakech, 400001, Morocco.

3Laboratory of Physiology Pharmacology and Environmental Health, Department of Biology, Faculty of Sciences Dhar Mehraz,Sidi Mohamed Ben Abdellah University, Fez, Morocco.

*E-mail: ghanimiridwane@gmail.com, ridwane.ghanimi@ced.uca.ma


Context: The infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global health emergency. The management of this crisis requires the discovery of new drugs able to cure or reduce the severity of SARS-CoV-2.

Aims: To explore the medicinal plants consumed by the rural population of Al-Haouz region against the emergence of the COVID-19, and to assess in silico the main phytochemicals present in the essential oils and the extracts of these medicinal plants, as potential inhibitors of the COVID-19 main protease (Mpro).

Methods: The survey was conducted through a semi-structured questionnaire among 85 respondents aged 30 years and above, in the Al-Haouz region, Morocco. AutoDock Vina, was used to assess the binding affinity of the phytochemicals to the Mpro.

Results: Eleven wild medicinal species were cited; 10 belonging to the Lamiaceae family and one to the Compositae family. Thymus saturejoides Coss., Artemisia herba-alba Asso.and Mentha suaveolens Ehrh. were respectively the three most cited species during the survey. The rosmarinic acid (-7.7 kcal/mol), hesperetin (-7.2 kcal/mol), gallocatechin (-7.2 kcal/mol) and cyasterone (-7.2 kcal/mol) have shown the higher inhibitory potential against covid-19 Mpro respectively.

Conclusions: In addition to their different recognized biological activities, the medicinal plants used in the Al-Haouz region have shown good inhibitory potential against SARAS-CoV-2 Mpro. Furthermore, the phytochemicals that exhibited the highest inhibitory potentials in this virtual study require further investigation in vitro and in vivo.

Keywords: COVID-19; ethnomedicine; medicinal plants; molecular docking; Morocco; SARS-CoV-2.


Contexto: La infección por el coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2) es una emergencia sanitaria mundial. El manejo de esta crisis requiere el descubrimiento de nuevos medicamentos capaces de curar o reducir la gravedad del SARS-CoV-2.

Objetivos: Explorar las plantas medicinales consumidas por la población rural de la región de Al-Haouz frente a la aparición del COVID-19, y evaluar in silico los principales fitoquímicos presentes en los aceites esenciales y los extractos de estas plantas medicinales, como potenciales inhibidores. de la proteasa principal COVID-19 (Mpro).

Métodos: La encuesta se realizó a través de un cuestionario semiestructurado entre 85 encuestados de 30 años o más, en la región de Al-haouz, Marruecos. Se utilizó AutoDock Vina para evaluar la afinidad de unión de los fitoquímicos al Mpro.

Resultados: Se citaron once especies medicinales silvestres; 10 pertenecientes a la familia Lamiaceae y una a la familia Compositae. Thymus saturejoides Coss., Artemisia herba-alba Asso. y Mentha suaveolens Ehrh. fueron, respectivamente, las tres especies más citadas durante la encuesta. El ácido rosmarínico (-7,7 kcal/mol), la hesperetina (-7,2 kcal/mol), la galocatequina (-7,2 kcal/mol) y la ciasterona (-7,2 kcal/mol) han mostrado el mayor potencial inhibitorio frente al covid-19 Mpro, respectivamente.

Conclusiones: Además de sus diferentes actividades biológicas reconocidas, las plantas medicinales utilizadas en la región de Al-Haouz han mostrado un buen potencial inhibitorio contra SARAS-CoV-2 Mpro. Además, los fitoquímicos que exhibieron los potenciales inhibidores más altos en este estudio virtual requieren más investigación in vitro e in vivo.

Palabras Clave: acoplamiento molecular; COVID-19; etnomedicina; Marruecos; plantas medicinales; SARS-CoV-2.

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Citation Format: Ghanimi R, Ouhammou A, El Atki Y, Cherkaoui M (2022) Molecular docking study of the main phytochemicals of some medicinal plants used against COVID-19 by the rural population of Al-Haouz region, Morocco. J Pharm Pharmacogn Res 10(2): 227–238.

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Volume 9, Suppl. 1 (MICPS 2021)

J Pharm Pharmacogn Res 9(Suppl. 1), (October) 2021

1st Makassar International Conference on Pharmaceutical Sciences

(MICPS 2021)

Empowering Natural Product in Drugs Discovery and Development

Faculty of Pharmacy Universitas Muslim Indonesia

Makassar, Indonesia

September 25-26, 2021

Conference Proceedings  [1.3 Mb]
Editing, design and realization: Gabino Garrido, Marisela Valdés, Xavier Garrido, Muammar Fawwaz, Aktsar Roskiana Ahmad
Editorial Scientific Council: Muammar Fawwaz, Aktsar Roskiana Ahmad, A. Emelda, Nurmaya Effendi

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Phaleria macrocarpa as anti-breast cancer agent

J Pharm Pharmacogn Res 9(6): 824-845, 2021.

Original article

Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl.leaf extract through in silico studies

[Potencial actividad contra el cáncer de mama del extracto de hoja de Phaleria macrocarpa (Scheff.) Boerl. mediante estudios in silico]

Yuyun Ika Christina 1, Wirdatun Nafisah2, Mochammad Fitri Atho’illah2, Muhaimin Rifa’i2, Nashi Widodo2, Muhammad Sasmito Djati2*

1Doctoral Program, Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, Indonesia.

2Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang 65145, East Java, Indonesia.

*E-mail: msdjati@ub.ac.id


Context: The development of apoptotic agent from natural plant products may have a beneficial effect as a promising candidate for cancer therapy. The study about the efficacy of Phaleria macrocarpa leaves on breast cancer is still limited.

Aims: To elucidate the molecular mechanisms underlying the anti-breast cancer activity of P. macrocarpa leaves extract by in silico analysis.

Methods: The compounds of the ethanol extract of P. macrocarpa were identified by Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS) analysis. Fourteen bioactive compounds of P. macrocarpa leaf were analyzed to determine the biological activity using Prediction of Activity Spectra for Substances (PASS) server. The network analysis was analyzed using STRING (https://string-db.org/). Twelve selected compounds were docked with several protein targets, including caspase 3, Bax and Bcl-2. Molecular docking was done by Pyrx 0.8 software and visualized by Discovery Studio software. The pharmacological properties of investigated bioactive compounds were analyzed using the SwissADME web server.

Results: The twelve from fourteen bioactive compounds of P. macrocarpa leaf have anticancer properties and might be expected to involve in p53 and PI3K/Akt signaling pathways related to cancer. The molecular docking result showed that sesamin from the lignans group has the best binding affinity to caspase-3 and Bax. Meanwhile, corymboside from the flavonoid group has the best binding affinity to Bcl-2.

Conclusions: The bioactive compounds of P. macrocarpa leaves extract might potentially modulate apoptosis and cell growth. Further research should be performed to validate the activity of P. macrocarpa bioactive compounds for target cancer development.

Keywords: anticancer activity; binding affinity; bioactive compound; molecular docking; Phaleria macrocarpa.

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Contexto: El desarrollo de un agente apoptótico a partir de productos vegetales naturales puede tener un efecto beneficioso como candidato prometedor para la terapia del cáncer. El estudio sobre la eficacia de las hojas de Phaleria macrocarpa en el cáncer de mama aún es limitado.

Objetivos: Dilucidar los mecanismos moleculares que subyacen a la actividad anticancerígena del extracto de hojas de P. macrocarpa mediante análisis in silico.

Métodos: Los compuestos del extracto etanólico de P. macrocarpa se identificaron mediante análisis de cromatografía líquida-espectrometría de masas de alta resolución (LC-HRMS). Catorce compuestos bioactivos de la hoja de P. macrocarpa fueron analizados para determinar la actividad biológica utilizando el servidor de Predicción de Espectros de Actividad para Sustancias (PASS). El análisis de la red se analizó utilizando STRING (https://string-db.org/). Se acoplaron doce compuestos seleccionados con varias dianas proteicas, incluida la caspasa 3, Bax y Bcl-2. El acoplamiento molecular se realizó con el software Pyrx 0.8 y se visualizó con el software Discovery Studio. Las propiedades farmacológicas de los compuestos bioactivos investigados se analizaron utilizando el servidor web SwissADME.

Resultados: Doce de los catorce compuestos bioactivos de la hoja de P. macrocarpa tienen propiedades anticancerígenas y se puede esperar que participen en las vías de señalización de p53 y PI3K/Akt relacionadas con el cáncer. El resultado del acoplamiento molecular mostró que la sesamina del grupo de los lignanos tiene la mejor afinidad de unión a la caspasa-3 y Bax. Mientras tanto, el corimbósido del grupo flavonoide tiene la mejor afinidad de unión a Bcl-2.

Conclusiones: Los compuestos bioactivos del extracto de hojas de P. macrocarpa podrían potencialmente modular la apoptosis y el crecimiento celular. Se deben realizar más investigaciones para validar la actividad de los compuestos bioactivos de P. macrocarpa para el desarrollo de dianas terapéuticas contra el cáncer.

Palabras Clave: acoplamiento molecular; actividad anticancerígena; afinidad de unión; compuesto bioactivo; Phaleria macrocarpa.

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Citation Format: Christina YI, Nafisah W, Atho'illah MF, Rifa'i M, Widodo N, Djati MS (2021) Anti-breast cancer potential activity of Phaleria macrocarpa (Scheff.) Boerl. leaf extract through in silico studies. J Pharm Pharmacogn Res 9(6): 824–845.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Anti-inflammatory molecular docking of Magnolia champaca flavonoids

J Pharm Pharmacogn Res 9(5): 584-597, 2021.

Original article

Ethnopharmacological study of flavonoid compounds in Magnolia champaca (L.) Baill. ex Pierre as anti-inflammatory agents by molecular docking

[Estudio etnofarmacológico de compuestos flavonoides en Magnolia champaca (L.) Baill. ex Pierre como agentes antiinflamatorios por acoplamiento molecular]

Khoirin Maghfiroh1,2, Sri Widyarti1, Jati Batoro1, Sutiman B. Sumitro1*

1Department of Biology, Faculty Mathematics and Natural Science, Brawijaya University, Malang 65145, East Java, Indonesia.

2Department ofFood Science and Technology, Faculty of Agriculture, Yudharta University, Pasuruan 67162, East Java, Indonesia.

*E-mail: sutiman@ub.ac.id


Context: Magnolia champaca (L.) Baill. ex Pierre has traditionally been used by the culture to prevent and cure the inflammatory disease.

Aims: To determine the benefit of M. champaca in the local community, especially in the treatment of tuberculosis, and investigate the potency of the flavonoid content of M. champaca as an anti-inflammatory agent through in silico analysis.

Methods: An ethnobotanical survey was conducted by structured interviews and responses in the Pamekasan district. The identification of flavonoid in selected plant was carried out from literature. Then, quercetin, (-)-epicatechin, and kaempferol were docked with protein targets including cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (p38 MAPK), nuclear factor kappa B (NF-κB), and phosphoinositide 3 kinases (PI3k). The ability of complex compounds was considered dependent on energy binding and the ability to bind native ligand to proteins.

Results: M. champaca exhibited the highest RFI value, indicated that this plant mainly used to treat tuberculosis symptoms in the local community. The compounds of quercetin and (-)-epicatechin can only be bound to a native ligand COX-2, NAG. The compounds quercetin, rutin, kaempferol, and (-)-epicatechin can then be bound to both the native proteins NF-κB and PI3K. Nevertheless, native ligand-protein p38 MAP-kinases cannot be bound by complex compounds like quercetin, rutin, kaempferol, and (-)-epicatechin.

Conclusions: The research offers proof for considering the flavonoid compound in M. champaca as a beneficial ligand complex throughout the treatment and prevention of inflammatory diseases. Further in vitro and in vivo studies could prove its therapeutic potential.

Keywords: anti-inflammatory candidate; ethnopharmacological study; Magnolia champaca; molecular docking.

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Contexto: Magnolia champaca (L.) Baill. ex Pierre ha sido utilizado tradicionalmente por la cultura para prevenir y curar enfermedades inflamatorias.

Objetivos: Determinar el beneficio de M. champaca en la comunidad local, especialmente en el tratamiento de la tuberculosis, e investigar la potencia del contenido de flavonoides de M. champaca como agente antiinflamatorio mediante análisis in silico.

Métodos: Se realizó una encuesta etnobotánica mediante entrevistas estructuradas y respuestas en el distrito de Pamekasan. La identificación de flavonoides en plantas seleccionadas se realizó a partir de la literatura. Luego, quercetina, (-) – epicatequina y kaempferol se acoplaron a proteínas dianas que incluían ciclooxigenasa-2 (COX-2), proteína quinasas activadas por mitógenos (p38 MAPK), factor nuclear kappa B (NF-κB) y fosfoinositida 3. quinasas (PI3k). Se consideró que la capacidad de los compuestos complejos dependía de la unión de energía y la capacidad de unir ligando nativo a proteínas.

Resultados: M. champaca exhibió el valor de RFI más alto, indicando que esta planta se usa principalmente para tratar síntomas de tuberculosis en la comunidad local. Los compuestos de quercetina y (-)-epicatequina solo pueden unirse a un ligando nativo COX-2, NAG. Los compuestos quercetina, rutina, kaempferol y (-)-epicatequina pueden unirse a las proteínas nativas NF-κB y PI3K. Sin embargo, las MAP-quinasas p38 ligando-proteína nativas no pueden unirse a compuestos complejos como quercetina, rutina, kaempferol y (-)-epicatequina.

Conclusiones: La investigación ofrece pruebas para considerar el compuesto flavonoide de M. champaca como un complejo ligando beneficioso en el tratamiento y prevención de enfermedades inflamatorias. Otros estudios in vitro e in vivo podrían demostrar su potencial terapéutico.

Palabras Clave: acoplamiento molecular; candidato antiinflamatorio; estudio etnofarmacológico; Magnolia champaca.

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Citation Format: Maghfiroh K, Widyarti S, Batoro J, Sumitro SB (2021) Ethnopharmacological study of flavonoid compounds in Magnolia champaca (L.) Baill. ex Pierre as anti-inflammatory agents by molecular docking. J Pharm Pharmacogn Res 9(5): 584–597.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Sea urchin peptides as multi-target inhibitor of NSCLC

J Pharm Pharmacogn Res 9(4): 484-496, 2021.

Original article

Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins

[Estudio de acoplamiento molecular de péptidos de erizo de mar (Arbacia lixula) como inhibidor de múltiples objetivos para proteínas asociadas al cáncer de pulmón de células no pequeñas (NSCLC)]

Muhammad Hermawan Widyananda1,2, Setyaki Kevin Pratama1, Rizky Senna Samoedra1, Fikriya Novita Sari1, Viol Dhea Kharisma2, Arif Nur Muhammad Ansori3, Yulanda Antonius4*

1Laboratory of Animal Physiology, Structure, and Growth, Biology Department, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia.

2Division of Molecular Biology and Genetics, Generasi Biologi Indonesia Foundation, Gresik, Indonesia.

3Doctoral Program in Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Faculty of Biotechnology, University of Surabaya, Surabaya, Indonesia.

*E-mail: yulandaantonius@staff.ubaya.ac.id


Context: Lung cancer is a type of cancer that causes the most deaths worldwide. The most common type of lung cancer is non-small cell lung cancer (NSCLC). Sea urchin (Arbacia lixula) has high potential as an anti-NSCLC agent.

Aims: To analyze the anticancer activity of peptides from A. lixula coelomic fluid in inhibiting the activity of NSCLC-related proteins.

Methods: Peptide modeling was performed using the PEP-FOLD3 web server. Proteins that have a crucial role in NSCLC progression were determined using KEGG pathway database. 3D protein structures such as EGFR, PI3K, BRAF V600E, and JAK3 were taken from the RCSB PDB database. Docking was performed using Autodock Vina software. Docking results analysis was carried out using Discovery Studio 2019 software.

Results: Some peptides bind to the active sites with low binding affinity. Peptide 10 binds to the active site of the EGFR with a binding affinity of -9 kcal/mol. Peptide 5 binds to the active sites of PI3K and BRAF V600E with binding affinity of -8.2 and -8.1 kcal/mol, respectively. Peptide 11 binds to the active site of JAK3 with a binding affinity of -8.1 kcal/mol. All of these peptides have lower binding affinity than ATP as the native ligand. Besides, these peptides also produce more hydrogen bonds than ATP, so they are predicted to be more stable.

Conclusions: Peptides 10, 5, and 11 have high potential as anti-NSCLC agents because they can inhibit the activity of proteins that play an essential role in the growth of NSCLC, namely EGFR, PI3K, BRAF V600E, and JAK3 through the competitive ATP inhibitor mechanism.

Keywords: Arbacia lixula; molecular docking; non-small cell lung cancer.

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Contexto: El cáncer de pulmón es un tipo de cáncer que causa la mayoría de las muertes en todo el mundo. El tipo más común de cáncer de pulmón es el cáncer de pulmón de células no pequeñas (NSCLC). El erizo de mar (Arbacia lixula) tiene un alto potencial como agente anti-NSCLC.

Objetivos: Analizar la actividad anticancerígena de péptidos del líquido celómico de A. lixula en la inhibición de la actividad de proteínas relacionadas con NSCLC.

Métodos: El modelado de péptidos se realizó utilizando el servidor web PEP-FOLD3. Las proteínas que tienen un papel crucial en la progresión del NSCLC se determinaron utilizando la base de datos de la vía KEGG. Las estructuras de proteínas 3D como EGFR, PI3K, BRAF V600E y JAK3 se tomaron de la base de datos RCSB PDB. El acoplamiento se realizó utilizando el software Autodock Vina. El análisis de los resultados del acoplamiento se llevó a cabo utilizando el software Discovery Studio 2019.

Resultados: Algunos péptidos se unen a los sitios activos con baja afinidad de unión. El péptido 10 se une al sitio activo del EGFR con una afinidad de unión de -9 kcal/mol. El péptido 5 se une a los sitios activos de PI3K y BRAF V600E con una afinidad de unión de -8,2 y -8,1 kcal/mol, respectivamente. El péptido 11 se une al sitio activo de JAK3 con una afinidad de unión de -8,1 kcal/mol. Todos estos péptidos tienen menor afinidad de unión que el ATP como ligando nativo. Además, estos péptidos también producen más enlaces de hidrógeno que el ATP, por lo que se prevé que sean más estables.

Conclusiones: Los péptidos 10, 5 y 11 tienen un alto potencial como agentes anti-NSCLC porque pueden inhibir la actividad de proteínas que juegan un papel esencial en el crecimiento del NSCLC, a saber, EGFR, PI3K, BRAF V600E y JAK3 a través del mecanismo inhibidor de ATP competitivo.

Palabras Clave: acoplamiento molecular; Arbacia lixula; cáncer de pulmón de células no pequeñas.

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Citation Format: Widyananda MH, Pratama SK, Samoedra RS, Sari FN, Kharisma VD, Ansori ANM, Antonius Y (2021) Molecular docking study of sea urchin (Arbacia lixula) peptides as multi-target inhibitor for non-small cell lung cancer (NSCLC) associated proteins. J Pharm Pharmacogn Res 9(4): 484–496.

© 2021 Journal of Pharmacy & Pharmacognosy Research (JPPRes)