TY - JOUR
T1 - Virtual screening of Indonesian herbal database as murine double minute-2 (MDM2) inhibitor
AU - Victory, Alexander
AU - Syahdi, Rezi Riadhi
AU - Yanuar, Arry
N1 - Publisher Copyright:
© 2018 Phcog.Net.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Background: Murine Double Minute-2 (MDM2) overexpression causes the p53 deficiency, so the role p53 as a cell regulator does not work in the case of cancer. Methods: In this study, virtual screening of Indonesian herbal database to discover MDM2 inhibitors was carried out. Autodock and Autodock Vina validated with Directory of Useful Decoy-Enhanced (DUD-E). Validation parameters were performed with Enrichment Factor, Receiver Operating Characteristics, and Area Under Curve. Results: The validation with the grid box 70x70x70 on Autodock resulting AUC value 0.72, while in Autodock Vina 0.43. Autodock Vina did not fulfilll the standard value but still used for comparison. Based on the virtual screening result, top ten compounds from Autodock are Nimolicinol, Jacoumaric acid, Isoarborinol, Lantic acid, Diosgenin, Theasaponin E1, Taraxasterol, Leucadenone C, Simiarenol, and Alpha-Amyrin were found to have strong interaction with MDM2, with binding energy (ΔG) ranging from -8.83 to -9.65 kcal/mol. The Autodock Vina screening resulted in the identification of Yuehchukene, Morusin, Cyanidin, Leucadenone C, Roxburghine-B, Ocidentoside, Beta-sitosterol, Curine, Withangulatin, and Jacoumaric acid as potential inhibitors with binding energy (ΔG) ranging from -8.7 to -9.4 kcal/mol. Conclusion: Jacoumaric acid and Leucadenone C were shown to interact with the active site in MDM2 at residues Leu54, Ile61, Met62, and Ile99.
AB - Background: Murine Double Minute-2 (MDM2) overexpression causes the p53 deficiency, so the role p53 as a cell regulator does not work in the case of cancer. Methods: In this study, virtual screening of Indonesian herbal database to discover MDM2 inhibitors was carried out. Autodock and Autodock Vina validated with Directory of Useful Decoy-Enhanced (DUD-E). Validation parameters were performed with Enrichment Factor, Receiver Operating Characteristics, and Area Under Curve. Results: The validation with the grid box 70x70x70 on Autodock resulting AUC value 0.72, while in Autodock Vina 0.43. Autodock Vina did not fulfilll the standard value but still used for comparison. Based on the virtual screening result, top ten compounds from Autodock are Nimolicinol, Jacoumaric acid, Isoarborinol, Lantic acid, Diosgenin, Theasaponin E1, Taraxasterol, Leucadenone C, Simiarenol, and Alpha-Amyrin were found to have strong interaction with MDM2, with binding energy (ΔG) ranging from -8.83 to -9.65 kcal/mol. The Autodock Vina screening resulted in the identification of Yuehchukene, Morusin, Cyanidin, Leucadenone C, Roxburghine-B, Ocidentoside, Beta-sitosterol, Curine, Withangulatin, and Jacoumaric acid as potential inhibitors with binding energy (ΔG) ranging from -8.7 to -9.4 kcal/mol. Conclusion: Jacoumaric acid and Leucadenone C were shown to interact with the active site in MDM2 at residues Leu54, Ile61, Met62, and Ile99.
KW - Cancer
KW - Docking
KW - Indonesian Herbal
KW - Inhibitor
KW - MDM2
KW - Virtual Screening
UR - http://www.scopus.com/inward/record.url?scp=85055796785&partnerID=8YFLogxK
U2 - 10.5530/pj.2018.6.203
DO - 10.5530/pj.2018.6.203
M3 - Article
AN - SCOPUS:85055796785
SN - 0975-3575
VL - 10
SP - 1184
EP - 1189
JO - Pharmacognosy Journal
JF - Pharmacognosy Journal
IS - 6
ER -