Computational Exploration of Bacterial Compounds Targeting Arginine-Specific Mono-Adp-Ribosyl-Transferase 1 (Art1): A Pathway to Novel Therapeutic Anticancer Strategies.

Cancer is a multifaceted and life-threatening disease characterized by the unregulated proliferation of malignant cells. Developing new therapies and diagnostic methods for cancer remains a critical focus of research. Proteins involved in cancer progression are being targeted to facilitate the discovery of effective biological treatments. Among these, the ART1 protein plays a critical role in promoting cancer progression, establishing it as a key target for drug therapy. Actinomycetes, known for their anticancer activity, were explored in this study for their potential to inhibit ART1. One hundred bioactive secondary metabolites derived from actinomycetes were subjected to in silico screening to evaluate their potential anticancer activity through inhibition of ART1. The three-dimensional structure of ART1 was generated using the SWISS-MODEL tool and validated through the Save server 6.0 and ProSa web. The structural stability of the ART1 protein was evaluated through molecular dynamics analysis using the iMod server. The potential active sites within the ART1 structure were mapped using the Computed Atlas of Surface Topography of Proteins (CASTp). Molecular docking and protein-ligand interaction studies were performed using AutoDock Vina. Additionally, pharmacophore modeling was conducted using the Pharmit server to identify promising compounds. Toxicity predictions and in silico drug-likeness assessments were carried out using Swiss-ADME and ADMET Lab which evaluate Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties. Molecular dynamics simulations results for the ART1 protein demonstrated high stability over time. Additionally, resistomycin, borrelidin, tetracycline, and oxytetracycline were identified as the top-ranking ligands, exhibiting binding energies between -8.9 kcal/mol and -9.3 kcal/mol. These ligands exhibited favorable pharmacophore profiles, drug-likeness, and ADMET properties, indicating their potential safety and efficacy in humans. In conclusion, the selected actinomycete-derived ligands show promise for further research and development as potential anticancer agents targeting ART1.