Synthesis and Cytotoxic Activity of 1,3-Selenazole-2-Amine Derivatives With Computational ADMET Profiling

Abstract

A set of newly developed 1,3-selenazole-2-amine derivatives (1–4) was prepared via a modified Hantzsch-type cyclization of appropriately substituted α-bromoacetophenones with selenourea under reflux conditions. The synthesized compounds were tested for cytotoxic activity in HT-29 (colon cancer), MCF-7 (breast cancer), and L929 (mouse fibroblast) cell lines using the MTT assay. The compounds induced weak to moderate cytotoxicity in MCF-7 cells. Among them, compound 4 showed cytotoxic activity with IC₅₀ value of 171.10 µM, while no appreciable activity was observed against HT-29 cells (IC₅₀ > 300 µM). Selectivity analysis demonstrated that compound 3 exhibited low toxicity toward healthy cells. In silico ADMET analysis indicated promising pharmacokinetic and physicochemical properties, including high gastrointestinal absorption, moderate lipophilicity, and compliance with drug-likeness rules, while predicting limited blood–brain barrier permeability. The BOILED-Egg model further supported high intestinal absorption and peripheral activity.