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In Silico Ligand-Based Methods Targeting Porcupine Receptor Inhibitors with Potential Anticancer Effect

Institute of Chemistry, Romanian Academy, Mihai Viteazul Avenue, 24, 300223 Timisoara, Romania
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Presented at the 22nd International Electronic Conference on Synthetic Organic Chemistry, 15 November–15 December 2018; Available Online: https://sciforum.net/conference/ecsoc-22
Proceedings 2019, 9(1), 19; https://doi.org/10.3390/ecsoc-22-05674
Published: 14 November 2018
PDF [467 KB, uploaded 18 March 2019]

Abstract

Porcupine is a protein belonging to the O-acyltransferase family, involved in the catalyzing of palmitoylation of wingless-related integration (WNT) proteins. WNT signaling has significant roles in many physiological functions, e.g., hematopoiesis, homeostasis, neurogenesis, and apoptosis. Anomalous WNT signaling has been observed to be related to tumor generation, and metabolic and neurodegenerative disorders. Therefore, compounds that inhibit this pathway are of great interest for the development of therapeutic approaches. For a better understanding of the common traits of such compounds, we have undertaken an in silico study in order to develop a valid ligand-based pharmacophore model based on a series of porcupine inhibitors. The best pharmacophore hypothesis found after the 3D QSAR validation process is represented by the following features: one hydrogen bond donor (D), three rings (R) and one hydrophobic centroid (H). The 3D-QSAR model obtained using the DRRRH hypothesis shows statistically significant parameters: correlation coefficients for the training set: R2 of 0.90, and a predictive correlation coefficient for the test set, Q2 of 0.86. The assessment of the pharmacophore model was also done and provided very reliable metrics values (Receiver Operating Characteristic—ROC of 1; Robust Initial Enhancement—RIE of 17.97). Thereby, we obtained valuable results which can be further used in the virtual screening process for the discovery of new active compounds with potential anticancer activity.
Keywords: Porcupine (PORCN) inhibitors; pharmacophore; 3D-QSAR Porcupine (PORCN) inhibitors; pharmacophore; 3D-QSAR
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Borota, A.; Crisan, L. In Silico Ligand-Based Methods Targeting Porcupine Receptor Inhibitors with Potential Anticancer Effect. Proceedings 2019, 9, 19.

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