Molecular Docking/ADME-TOX-Based Analysis for New Anti-Colorectal Cancer Through Peroxiredoxin 1 Inhibition

Colorectal cancer ranks as the third most prevalent form of cancer on a global scale. The abnormal expression of Peroxiredoxin 1, or PRDX1, plays an important role in cancer progression and tumor cell survival. This makes inhibiting this protein a promising target for colorectal cancer treatment. In order to develop effective PRDX1 inhibitors, a drug design investigation based on computational methods was carried out using a collection of recently synthesized compounds derived from two main chemical base structures: C-5 sulfenylated amino uracils and 1,2,3-triazole benzothiazole derivatives. To obtain the PRDX1 protein PDB ID: 7WET, molecular docking was performed on the studied compounds in combination with PRDX1. The 1,2,3-triazole benzothiazole derivatives showed interesting docking results. For instance, nine promising candidates were distinguished by their formation of better stable complexes with PRDX1 in terms of E (binding) from −7.0 to −7.3 kcal/mol, namely, 7WET-L18, 7WET-L17, 7WET-L25, 7WET-L19, 7WET-L20, 7WET-L26, 7WET-L22, 7WET-L23, and 7WET-L24, as well as an E of −6.8 kcal/mol for Celastrol, a known PRDX1 inhibitor. Moreover, an extensive evaluation of ADME-TOX was performed to predict the pharmacokinetic, pharmacodynamic, and toxicological properties of the compounds studied. The findings offer significant support for the prospective application of these analogs in the fight against colorectal cancer.