Computational Exploration of Adenylyl Cyclase Type 2 Inhibition by Oleandrin Glycosides via Molecular Docking Studies

Syed Aun Muhammad *

Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan, Pakistan.

Syeda Tahira Qousain Naqvi

Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan, Pakistan.

Tahir Naqqash

Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan, Pakistan.

Sadaf Noor

Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan, Pakistan.

*Author to whom correspondence should be addressed.


Adenylyl cyclase type 2 (ADCY2) is an enzyme linked to membranes that is implicated in the spread of many cancer types and tumors. As such, it may be a target for therapeutic intervention. Using molecular docking, we examined how these compounds bound to ADCY2. Cancer is treated with chemotherapy drugs; however, these drugs frequently have serious side effects. The current study aims to computationally assess the anticancer potential of natural glycosides, such as oleandrin. We used Phyre to evaluate the quality of the protein model after modeling the structure of adenylyl cyclase. For the binding affinity analysis, the Molecular Operating Environment (MOE) program was utilized. The ligand used to dock with the ADCY2 molecule was oleandrin. Oleandrin exhibited a strong binding affinity towards the ADCY2 target molecule, as demonstrated by its binding energy of -97.7513 kcal/mol. The anticancer potential of oleandrin is indicated by its strong binding affinity for the adenylyl cyclase protein target. The findings of this study suggest that oleandrin may have been used in cancer treatment as an ADCY2 inhibitor. This research would contribute to the development of novel anti-cancer drugs, expanding the range of available cancer treatments.

Keywords: ADCY2, lead compounds, oleandrin, anticancer molecules, computational analysis

How to Cite

Muhammad, S. A., Naqvi, S. T. Q., Naqqash, T., & Noor, S. (2024). Computational Exploration of Adenylyl Cyclase Type 2 Inhibition by Oleandrin Glycosides via Molecular Docking Studies. Asian Journal of Biotechnology and Genetic Engineering, 7(1), 1–7. Retrieved from


Download data is not yet available.


Shillitoe E., et al. Genome-wide analysis of oral cancer—early results from the cancer genome anatomy project. Oral Oncology. 2000;36(1):8-16.

Bird A. DNA methylation patterns and epigenetic memory. Genes & Development. 2002;16(1):6-21.

Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nature Reviews Cancer,. 2011;11(10):726-734.

Li Y., et al. Molecular cloning, sequence identification, and gene expression analysis of bovine ADCY2 gene. Molecular Biology Reports. 2014. 41:3561-3568.

Herman JG., et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proceedings of the National Academy of Sciences. 1994;91(21): 9700-9704.

Herman JG., et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proceedings of the National Academy of Sciences. 1998;95(12):6870-6875.

Catto JW., et al. Promoter hypermethylation is associated with tumor location, stage, and subsequent progression in transitional cell carcinoma. Journal of Clinical Oncology, 2005;23(13):2903-2910.

Zheng M., et al. TRIO amplification and abundant mRNA expression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. The American Journal of Pathology. 2004;165(1):63-69.

Pfeifer GP. Defining driver DNA methylation changes in human cancer. International Journal of Molecular Sciences. 2018;19(4):1166.

Newman RA., et al. Antiviral effects of oleandrin. Journal of Experimental Pharmacology. 2020:503-515.

Zhai J., et al. Oleandrin: a systematic review of its natural sources, structural properties, detection methods, pharmacokinetics and toxicology. Frontiers in Pharmacology. 2022;13:822726.

Kanwal N., et al. Oleandrin: A bioactive phytochemical and potential cancer killer via multiple cellular signaling pathways. Food and Chemical Toxicology. 2020; 143:111570.

Langford SD, Boor P.J. Oleander toxicity: an examination of human and animal toxic exposures. Toxicology. 1996;109(1):1-13.

Aqeel MT., et al. In silico approach for the development of phenolic derivatives as potential anti-angiogenic agents against lysyl oxidase-like 2 enzyme. Future Journal of Pharmaceutical Sciences. 2022;8(1):1-11.

Kolla L., et al. The case for AI-driven cancer clinical trials–The efficacy arm in silico. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer.2021;1876(1): 188572.

Bajorath J. Integration of virtual and high-throughput screening. Nature Reviews Drug Discovery. 2002;1(11):882-894.

Varela‐Rial AM, Majewski, G. De Fabritiis, Structure based virtual screening: Fast and slow. Wiley Interdisciplinary Reviews: Computational Molecular Science. 2022;12(2):e1544.

Kelley LA., et al. The Phyre2 web portal for protein modeling, prediction and analysis. Nature Protocols. 2015;10(6): 845-858.

Muhammad SA., et al. Insilico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors. Computational Biology and Chemistry. 2014;51:71-82.

Muhammed MT, Aki-Yalcin E. Molecular docking: principles, advances, and its applications in drug discovery. Lett Drug Des Discov. 2022;19.

Abbas SZ, Qadir MI, Muhammad SA. Systems-level differential gene expression analysis reveals new genetic variants of oral cancer. Scientific Reports. 2020;10(1): 14667.

Chen SL., et al. Prognosis and regulation of an adenylyl cyclase network in acute myeloid leukemia. Aging (Albany NY). 2020;12(12):11864.

Yang J., et al., Identification of adenylate cyclase 2 methylation in bladder cancer with implications for prognosis and immunosuppressive microenvironment. Frontiers in Oncology. 2022;12: 1025195.

Zhao G., et al., Estrogen promotes cAMP production in mesenchymal stem cells by regulating ADCY2. International journal of stem cells. 2020;13(1):55-64.

Abbas SZ., et al., In silico Study of Adenylyl Cyclase Type 2 Inhibitors. GSJ. 2021;9(4).

Zaid H., et al., Physicochemical properties of natural based products versus synthetic chemicals. The Open Nutraceuticals Journal. 2010;3(1).

Francischini CRD., et al., Antitumor effects of oleandrin in different types of cancers: Systematic review. Toxicon. 2022;216:15-27.

Ni D., et al., Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander. Journal of Experimental Therapeutics and Oncology. 2002;2(5):278-285.

Majolo F., et al., Medicinal plants and bioactive natural compounds for cancer treatment: Important advances for drug discovery. Phytochemistry Letters. 2019;31:196-207.

Frye M., et al., Genomic gain of 5p15 leads to over-expression of Misu (NSUN2) in breast cancer. Cancer Letters 2010; 289(1):71-80.