<abstract xmlns="http://www.w3.org/1999/xhtml">

<p><italic>Markhamia tomentosa</italic> crude extract and fractions exhibited potent growth inhibitory effects capable to induce apoptosis in cervical (HeLa) cancer cell line via <italic>in vitro</italic> model. Presently, interaction of <italic>M. tomentosa</italic> phytoconstituents with molecular drug targets to exert its anticancer property is evaluated via <italic>in silico</italic> study. Identified phytoconstituents from <italic>M. tomentosa</italic> were retrieved from PubChem database and docked in active sites of HPV 16 E6, caspase -3 and caspase -8 targets using AutoDockVina from PyRx software. Screening for druglikeness; and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions was carried out with the use of SwissADME and pkCSM web servers. Standard melphalan and co-crystallized ligands of caspases -3 and -8 enzymes were used to validate protein-ligand interactions. Molecular dynamic simulation was used to validate the stability of the hit molecules complexed with caspases -3 and -8. All identified phytoconstituents from <italic>M. tomentosa</italic> showed binding affinity for HPV with docking scores range of - 5.4 to -2.6 kcal/mol. Ajugol, carnosol, luteolin and phytol showed good docking energy range of -6.8 to -3.6 kcal/mol; and -4.8 to -1.9 kcal/mol for the active sites of caspases -3 and -8 targets respectively. Based on docking scores; drug-likeliness; and ADMET predictions; luteolin and carnosol were selected as hit compounds. These molecules were found to be stable within the binding site of caspase -3 target throughout the 40ns simulation time. These findings identified hit ligands from <italic>M. tomentosa</italic> phytoconstituents that inhibit HPV 16 E6 oncogene expression with stimulation of caspases -3 and -8 targets.</p>
</abstract>

Markhamia tomentosa crude extract and fractions exhibited potent growth inhibitory effects capable to induce apoptosis in cervical (HeLa) cancer cell line via in vitro model. Presently, interaction of M. tomentosa phytoconstituents with molecular drug targets to exert its anticancer property is evaluated via in silico study. Identified phytoconstituents from M. tomentosa were retrieved from PubChem database and docked in active sites of HPV 16 E6, caspase -3 and caspase -8 targets using AutoDockVina from PyRx software. Screening for druglikeness; and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions was carried out with the use of SwissADME and pkCSM web servers. Standard melphalan and co-crystallized ligands of caspases -3 and -8 enzymes were used to validate protein-ligand interactions. Molecular dynamic simulation was used to validate the stability of the hit molecules complexed with caspases -3 and -8. All identified phytoconstituents from M. tomentosa showed binding affinity for HPV with docking scores range of - 5.4 to -2.6 kcal/mol. Ajugol, carnosol, luteolin and phytol showed good docking energy range of -6.8 to -3.6 kcal/mol; and -4.8 to -1.9 kcal/mol for the active sites of caspases -3 and -8 targets respectively. Based on docking scores; drug-likeliness; and ADMET predictions; luteolin and carnosol were selected as hit compounds. These molecules were found to be stable within the binding site of caspase -3 target throughout the 40ns simulation time. These findings identified hit ligands from M. tomentosa phytoconstituents that inhibit HPV 16 E6 oncogene expression with stimulation of caspases -3 and -8 targets.

Phytoconstituents from <italic>Markhamia tomentosa</italic> Bind To HPV Oncoprotein with Apoptogenic Potential: A Molecular Modeling Approach

Department of Pharmacognosy, Faculty of Pharmacy

University of Lagos, College of Medicine Campus

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences

Chemogenomics Unit, Department of Biochemistry

Annals of Science and Technology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Phytoconstituents from  Bind To HPV Oncoprotein with Apoptogenic Potential: A Molecular Modeling Approach

Markhamia tomentosa crude extract and fractions exhibited potent growth inhibitory effects capable to induce apoptosis in cervical (HeLa) cancer cell line via...

Phytoconstituents from Markhamia tomentosa Bind To HPV Oncoprotein with Apoptogenic Potential: A Molecular Modeling Approach

Publicado en línea: 07 dic 2021

Páginas: 28 - 46

Recibido: 31 ago 2021

Aceptado: 28 oct 2021

DOI: https://doi.org/10.2478/ast-2021-0008

Palabras clave
HPV16 E6, Caspases, Molecular docking, Luteolin, Carnosol

© 2021 Mutiat B. Ibrahim et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Phytoconstituents from Markhamia tomentosa Bind To HPV Oncoprotein with Apoptogenic Potential: A Molecular Modeling Approach

Publicado en línea: 07 dic 2021

Páginas: 28 - 46

Recibido: 31 ago 2021

Aceptado: 28 oct 2021

DOI: https://doi.org/10.2478/ast-2021-0008

Palabras claveHPV16 E6, Caspases, Molecular docking, Luteolin, Carnosol

© 2021 Mutiat B. Ibrahim et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Palabras clave
HPV16 E6, Caspases, Molecular docking, Luteolin, Carnosol