PRDX1 inhibition based on Molecular docking and ADME-TOX study Using new anti-colorectal cancer compounds

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 applied 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. Towards the PRDX1 protein PDB ID: 7WET, a molecular docking was performed on the studied compounds in complex with PRDX1. The 1,2,3-triazole benzothiazole derivatives show interesting docking results. in which nine top hits 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. And E of -6.8 kcal/mol for Celastrol as a known PRDX1 inhibitor, Moreover, a comprehensive assessment of ADME-TOX was conducted in order to anticipate the pharmacokinetic, pharmacodynamic , and toxicological characteristics of the compounds under investigation. The results obtained provide substantial backing for the potential use of these analogues in combating colorectal cancer.