Repurposing of FDA Approved Drugs and Neuropep peptides as Anticancer Agents Against ErbB1 and ErbB2

Abstract

ErbB1 and ErbB2 are the most important biological targets in cancer drug discovery and development of dual inhibitors for the cancer therapy. FDA approved drugs and Neuropep peptides were used to fit into the ATP binding site of the tyrosine kinases; ErbB1 and ErbB2 proteins. Cytoscape, iGEMDOCK, HPEPDOCK and DataWarrior softwares were used to study the role of these agents as anticancer drugs. Eleven FDA approved drugs and eleven Neuropep peptides showed the strongest 2D interactions and significant binding energy with the proteins. Invitro MTT anticancer assay revealed that, the test compounds, peptide YSFGL and doxorubicin showed significant IC₅₀ value (µM) of 26.417±0.660 and 7.675±0.278 respectively which are compared with the lapatinib standard IC₅₀ value (µM) of 2.380±0.357 against A549 cells and IC₅₀ value (µM) of 39.047±0.770 and 8.313±0.435 respectively which are compared with the lapatinib standard IC₅₀ value (µM) of 3.026±0.180 against MDA-MB-231 cells.

Key words

cytoscape - igemdock - hpepdock - datawarrior - invitro proliferation assay.

Publikationsverlauf

Eingereicht: 11. Januar 2023

Angenommen: 30. Januar 2023

Artikel online veröffentlicht:
17. April 2023

• References

• 1 Iheagwam FN, Ogunlana OO, Ogunlana OE. et al. Potential anti-cancer flavonoids isolated from Caesalpinia bonduc young twigs and leaves: molecular docking and in silico studies. Bioinformatics and Biology Insights 2019; 13: 1177932218821371
• 2 Chakravarti B, Maurya R, Siddiqui JA. et al. In vitro anti-breast cancer activity of ethanolic extract of Wrightia tomentosa: role of pro-apoptotic effects of oleanolic acid and urosolic acid. Journal of Ethnopharmacology 2012; 142: 72-79
• 3 Kakde D, Jain D, Shrivastava V. et al. Cancer therapeutics-opportunities, challenges and advances in drug delivery. Journal of Applied Pharmaceutical Science 2011; 01-10
• 4 Roskoski R. The ErbB/HER family of protein-tyrosine kinases and cancer. Pharmacological Research 2014; 79: 34-74
• 5 Roskoski R. ErbB/HER protein-tyrosine kinases: Structures and small molecule inhibitors. Pharmacological Research 2014; 87: 42-59
• 6 Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010; 141: 1117-1134
• 7 Ahsan A, Ramanand SG, Bergin IL. et al. Efficacy of an EGFR-specific peptide against EGFR-dependent cancer cell lines and tumor xenografts. Neoplasia 2014; 16: 105-W2
• 8 Roskoski R. Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. Pharmacological Research 2019; 139: 395-411
• 9 Normanno N, De Luca A, Bianco C. et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 2006; 366: 2-16
• 10 Deng Y, Li J. Rational Optimization of Tumor Suppressor-Derived Peptide Inhibitor Selectivity between Oncogene Tyrosine Kinases ErbB1 and ErbB2. Archiv Der Pharmazie 2017; 350: 1700181
• 11 Patnaik SK, Chandrasekar MJN, Nagarjuna P. et al. Targeting of ErbB1, ErbB2, and their Dual Targeting Using Small Molecules and Natural Peptides: Blocking EGFR Cell Signaling Pathways in Cancer: A Mini Review. Mini Reviews in Medicinal Chemistry. 2022
• 12 Zhong L, Li Y, Xiong L. et al. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduction and Targeted Therapy 2021; 6: 1-48.
• 13 Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers 2017; 9: 52
• 14 Spector NL, Xia W, Burris H. et al. Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. Journal of Clinical Oncology 2005; 23: 2502-2512
• 15 Mine Y, Munir H, Nakanishi Y. et al. Biomimetic peptides for the treatment of cancer. Anticancer Research 2016; 36: 3565-3570
• 16 Wood ER, Truesdale AT, McDonald OB. et al. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res 2004; 64: 6652-6659
• 17 Aertgeerts K, Skene R, Yano J. et al. Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. Journal of Biological Chemistry 2011; 286: 18756-18765
• 18 Berman HM, Westbrook J, Feng Z. et al. The protein data Bank nucleic acids research. 2000. Europe PMC Free Article][Abstract][Google Scholar] 2021; 235-242
• 19 Wang Y, Wang M, Yin S. et al. NeuroPep: a comprehensive resource of neuropeptides. Database 2015; 2015
• 20 Killcoyne S, Carter GW, Smith J. et al. Cytoscape: a community-based framework for network modeling. Methods Mol Biol 2009; 563: 219-239
• 21 Chen S. Network analysis of Urocortins. Neuroendocrinology Letters 2016; 37: 461–466
• 22 Hsu K-C, Chen Y-F, Lin S-R. et al. iGEMDOCK: a graphical environment of enhancing GEMDOCK using pharmacological interactions and post-screening analysis. BMC Bioinformatics 2011; 12: 1-11.
• 23 Zhou P, Jin B, Li H. et al. HPEPDOCK: a web server for blind peptide–protein docking based on a hierarchical algorithm. Nucleic Acids Research 2018; 46: W443-W450
• 24 Sander T, Freyss J, von Korff M. et al. DataWarrior: an open-source program for chemistry aware data visualization and analysis. Journal of Chemical Information and Modeling 2015; 55: 460-473
• 25 Meerloo JV, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Cancer cell culture. Springer; 2011: 237-245