In silico Investigation of the Anticancer Activity of Natural Isoquinoline Alkaloids Targeting the Monoamine Oxidase a Enzyme

Authors

Reham A. Al-Anssari, Department of Pharmacognosy and Medicinal Plants, College of Pharmacy, University of Basra, Basra, IraqFollow
Anwar H. Ali, Department of Pharmacognosy and Medicinal Plants, College of Pharmacy, University of Basra, Basra, IraqFollow
Ola Adel Al-Saad, Department of Pharmacognosy and medicinal plants, College of Pharmacy, University of Basra, Basra, IraqFollow
Shaker A.N. Al-Jadaan, Department of pharmaceutical chemistry, College of Pharmacy, University of Basra, Basra, IraqFollow

Corresponding Author

Reham A. Al-Anssari

Authors ORCID

Reham A. Al-Anssari: https://orcid.org/: 0000-0001-6880-2120

Anwar H. Ali: https://orcid.org/0000-0002-6637-2064

Ola Adel Al-Saad: https://orcid.org/0000-0002-2968-734X

Shaker A.N.Al-Jadaan: https://orcid.org/0000-0003-0587-8632

Abstract

Monoamine oxidase A (MAO-A) has recently been identified as a candidate for cancer therapy due to its roles in tumor development and growth. Conventional approaches for the discovery of MAO-A inhibitors are both costly and time-consuming. The objective of this work was to apply in silico methods to predict natural isoquinoline alkaloids capable of acting as potent MAO-A inhibitors, and to establish this class of compounds as potential sources of a cost-effective anticancer therapy. Twenty-one natural isoquinoline alkaloids were subjected to a multistep computer-aided drug discovery protocol. The compounds were initially screened for pharmacokinetic (ADME), toxicity, and drug-likeliness properties by computational screening tools. chemoinformatic analyses were made to predict molecular targets and subsequently, molecular docking studies was performed to evaluate binding interaction with MAO-A enzyme, focusing on docking scores and root mean square deviation (RMSD) values. The majority of the tested compounds showed good ADME characteristics and were predicted to be non-toxic, except compound 6, which showed a potentially toxic profile. Target prediction results indicated high selectivity for MAO-A of all 21 compounds. Analysis of molecular docking results showed high binding affinity of the studied compounds with root mean square deviation (RMSD) values of 0.4454–2.3 Å and binding free energy (S-score) of −4.5877 to −6.3278 kcal/mol. These findings reveal several isoquinoline alkaloids with strong MAO-A binding and favorable pharmacokinetic and safety profiles, especially compound 2. This supports their potential as anticancer leads and highlights the value of further in vitro and in vivo studies to confirm therapeutic applicability.

Recommended Citation

Al-Anssari, Reham A.; Ali, Anwar H.; Al-Saad, Ola Adel; and Al-Jadaan, Shaker A.N. (2025), In silico Investigation of the Anticancer Activity of Natural Isoquinoline Alkaloids Targeting the Monoamine Oxidase a Enzyme, AUIQ Complementary Biological System: Vol. 2: Iss. 2, 77-89.
DOI: https://doi.org/10.70176/3007-973X.1038
Available at: https://acbs.alayen.edu.iq/journal/vol2/iss2/6

Digital Object Identifier (DOI)

10.70176/3007-973X.1038