ORIGINAL RESEARCH article
Front. Chem.
Sec. Theoretical and Computational Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1533026
In Silico Molecular Studies of Phosphinogold(I) Thiocarbohydrate Complexes: Insights into Multi-target Anticancer Mechanisms
Provisionally accepted
- 1University of Cape Coast, Cape Coast, Ghana
- 2University of Johannesburg, Johannesburg, Gauteng, South Africa
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This study employed in silico methods to investigate the anticancer potential and mechanisms of twenty novel phosphinogold(I) thiocarbohydrate complexes. Molecular docking and Prime MM-GBSA screening of seventeen cancer-related protein targets, including Human Double Minute 2 protein (HDM2), DNA methyltransferase-1 (DNMT1), Protein Kinase B (AKT2), and Poly (ADP-ribose) polymerase 1 (PARP-1), revealed strong binding affinities for several complexes, often surpassing native ligands. All the complexes except 16, 18 and 19 exhibited strong binding affinity with one or two cancer protein targets compared to native ligands. Complex 9 emerged as the best candidate, demonstrating promising binding affinity particularly against AKT2 (-82.40 kcal/mol) and PARP-1(-75.7 kcal/mol). Further molecular dynamics simulations of complex 9 with PARP-1 and AKT2 revealed distinct binding profiles. A more stable interaction with PARP-1, suggesting its potential for disrupting DNA repair mechanisms and highlighting PARP-1 as a particularly promising therapeutic target of complex 9 has been proven. These findings provide valuable insights into multi-target anticancer mechanisms, with a particular emphasis on complex 9 as a potential PARP-1 inhibitor, and guide future optimization and experimental validation of these novel gold-based complexes. Binuclear complexes generally exhibited higher affinities than mononuclear counterparts, particularly for DNMT1 and HDM2. Complex 13 demonstrated high in vitro activity against prostate, colon and breast cancer cell lines (IC 50 = 0.03, 0.25, and 0.07µM respectively) collaborating with a significant interaction with HER2 (-71.15 kcal/mol binding affinity) in silico. While acetylation decreased binding affinity; it
Keywords: Anticancer activity, Cytotoxicity, MM-GBSA, molecular docking, Structureactivity relationship, Thiocarbohydrate Phosphinogold(I) complexes
Received: 22 Nov 2024; Accepted: 08 May 2025.
Copyright: © 2025 Adokoh, Khalil, Asiamah and Darkwa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Christian Kweku Adokoh, University of Cape Coast, Cape Coast, Ghana
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